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Background: In early 2020, COVID-19 pandemic has mobilized researchers in finding new remedies including repurposing of medicinal plant products focusing on direct-acting antiviral and host-directed therapies. In this study, we performed an in vitro investigation on the standardized Marantodes pumilum extract (SKF7®) focusing on anti-SARS-CoV-2 and anti-inflammatory activities. Methods: Anti-SARS-CoV-2 potential of the SKF7® was evaluated in SARS-CoV-2-infected Vero E6 cells and SARS-CoV-2-infected A549 cells by cytopathic effect-based assay and RT-qPCR, respectively. Target based assays were performed on the SKF7® against the S1-ACE2 interaction and 3CL protease activities. Anti-inflammatory activity of the SKF7® was evaluated by nitric oxide inhibitory and TLR2/TLR4 receptor blocker assays. Results: The SKF7® inhibited wild-type Wuhan (EC50 of 21.99 µg/mL) and omicron (EC50 of 16.29 µg/mL) SARS-CoV-2 infections in Vero-E6 cells. The SKF7® also inhibited the wild-type SARS-CoV-2 infection in A549 cells (EC50 value of 6.31 µg/mL). The SKF7® prominently inhibited 3CL protease activity. The SKF7® inhibited the LPS induced-TLR4 response with the EC50 of 16.19 µg/mL. Conclusions: In conclusion, our in vitro study highlighted anti-SARS-CoV-2 and anti-inflammatory potentials of the SKF7®. Future pre-clinical in vivo studies focusing on antiviral and immunomodulatory potentials of the SKF7® in affecting the COVID-19 pathogenesis are warranted. [ABSTRACT FROM AUTHOR]

Hemisynthesis makes it possible to improve the activity or reduce the toxicity of a biocompound by modifying or adding peripheral groups. Catechin present in different plant species was known for its moderate anti-malarial and anti-SARS-CoV-2 activities. The aim of this work was focused on the identification of new compounds with potential anti-SARS-CoV-2 and/or anti-malarial activities, evaluated through In silico simulation. A polyphenol pharmacophore model, based on (+)-catechin (1) was virtually constructed using previously reported inhibitors. N- and/or S-heterocyclic fragments were inserted on the backbone of (+)-catechin and 12 pharmacophore hypotheses were studied. This study targeted 3 proteins biologically responsible for SARS-CoV-2 (PDB ID: 7JYC, 6M0J, and 6HZD) and one protein responsible for malaria (PDB ID: 3SRJ). Molecular docking had shown that the new catechin-aldehyde candidates have good Ligand-Protein affinity in terms of free energy compared to the study reference Narlaprevir and Artesunate for SARS-CoV-2 and malaria respectively. Theoretically, most compounds didn't show toxicity except compounds 2a, 2i, and 2k, exhibiting hepatotoxic activity. Molecular dynamics was used to prove and assess their binding stability to the target protein for each activity. The 3SRJ-2f and 6HZD-2l structures were selected for anti-malarial and anti-SARS-CoV-2 activity respectively. The 3SRJ-2f and 6HZD-2l complexes showed stable interactions to 100 ns between the inhibitor fragments and the residual amino acids of the protein. To conclude, these novel compounds are probably to become promising lead molecules for the development of effective anti-SARS-CoV-2 and/or anti-malarial of all drugs. [ABSTRACT FROM AUTHOR]

Abstract Background In early 2020, COVID-19 pandemic has mobilized researchers in finding new remedies including repurposing of medicinal plant products focusing on direct-acting antiviral and host-directed therapies. In this study, we performed an in vitro investigation on the standardized Marantodes pumilum extract (SKF7®) focusing on anti-SARS-CoV-2 and anti-inflammatory activities. Methods Anti-SARS-CoV-2 potential of the SKF7® was evaluated in SARS-CoV-2-infected Vero E6 cells and SARS-CoV-2-infected A549 cells by cytopathic effect-based assay and RT-qPCR, respectively. Target based assays were performed on the SKF7® against the S1-ACE2 interaction and 3CL protease activities. Anti-inflammatory activity of the SKF7® was evaluated by nitric oxide inhibitory and TLR2/TLR4 receptor blocker assays. Results The SKF7® inhibited wild-type Wuhan (EC50 of 21.99 µg/mL) and omicron (EC50 of 16.29 µg/mL) SARS-CoV-2 infections in Vero-E6 cells. The SKF7® also inhibited the wild-type SARS-CoV-2 infection in A549 cells (EC50 value of 6.31 µg/mL). The SKF7® prominently inhibited 3CL protease activity. The SKF7® inhibited the LPS induced-TLR4 response with the EC50 of 16.19 µg/mL. Conclusions In conclusion, our in vitro study highlighted anti-SARS-CoV-2 and anti-inflammatory potentials of the SKF7®. Future pre-clinical in vivo studies focusing on antiviral and immunomodulatory potentials of the SKF7® in affecting the COVID-19 pathogenesis are warranted.

Abstract Background Natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vaccination triggers antibody production against key viral antigens. However, there is limited evidence on the levels of antibodies produced in naturally infected individuals compared to those vaccinated in Ethiopia. Therefore, we aimed to detect and compare SARS-CoV-2 antibodies produced by naturally infected and vaccinated individuals. Materials and methods We conducted a multicenter cross-sectional study among a total of 355 naturally infected and 355 vaccinated individuals from November 2022 to April 2023 at 10 selected health facilities in Addis Ababa, Ethiopia. We enrolled the participants consecutively upon their arrival at health facilities until the required sample size was achieved. We used a structured questionnaire to collect data on the demographic and clinical characteristics of the participants. We also collected 3–5 ml of blood samples from all participants and tested for anti-Spike (anti-S) and anti-nucleocapsid (anti-N) antibodies using Cobas 6000. We utilized frequency, mean, or median to describe the data, the Mann-Whitney U test to compare groups, and a generalized linear regression model to assess factors associated with anti-S antibody concentration. We analyzed the data with SPSS version 26, and the level of significance was set at P-value

Abstract Background The high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), has triggered global health and economic concerns. The absence of specific antiviral treatments and the side effects of repurposed drugs present persistent challenges. This study explored a promising antiviral herbal extract against SARS-CoV-2 from selected Thai medicinal plants based on in vitro efficacy and evaluated its antiviral lead compounds by molecular docking. Methods Twenty-two different ethanolic-aqueous crude extracts (CEs) were rapidly screened for their potential activity against porcine epidemic diarrhea virus (PEDV) as a surrogate using a plaque reduction assay. Extracts achieving ≥ 70% anti-PEDV efficacy proceeded to the anti-SARS-CoV-2 activity test using a 50% tissue culture infectious dose method in Vero E6 cells. Molnupiravir and extract-free media served as positive and negative controls, respectively. Potent CEs underwent water/ethyl acetate fractionation to enhance antiviral efficacy, and the fractions were tested for anti-SARS-CoV-2 performance. The fraction with the highest antiviral potency was identified using liquid chromatography–high-resolution mass spectrometry (LC–HRMS). Molecular docking analyses of these compounds against the main protease (Mpro) of SARS-CoV-2 (6LU7) were performed to identify antiviral lead molecules. The top three hits were further evaluated for their conformational stability in the docked complex using molecular dynamics (MD) simulation. Results The water fraction of mulberry (Morus alba Linn.) leaf CE (WF-MLCE) exhibited the most potent anti-SARS-CoV-2 efficacy with low cytotoxicity profile (CC50 of ~ 0.7 mg/mL), achieving 99.92% in pre-entry mode and 99.88% in postinfection treatment mode at 0.25 mg/mL. Flavonoids and conjugates were the predominant compounds identified in WF-MLCE. Molecular docking scores of several flavonoids against SARS-CoV-2 Mpro demonstrated their superior antiviral potency compared to molnupiravir. Remarkably, myricetin-3-O-β-D-galactopyranoside, maragrol B, and quercetin 3-O-robinobioside exhibited binding energies of ~ − 9 kcal/mol. The stability of each ligand–protein complex of these compounds with the Mpro system showed stability during MD simulation. These three molecules were pronounced as antiviral leads of WF-MLCE. Given the low cytotoxicity and high antiviral potency of WF-MLCE, it holds promise as a candidate for future therapeutic development for COVID-19 treatment, especially considering its economic and pharmacological advantages.

Background: Natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vaccination triggers antibody production against key viral antigens. However, there is limited evidence on the levels of antibodies produced in naturally infected individuals compared to those vaccinated in Ethiopia. Therefore, we aimed to detect and compare SARS-CoV-2 antibodies produced by naturally infected and vaccinated individuals. Materials and methods: We conducted a multicenter cross-sectional study among a total of 355 naturally infected and 355 vaccinated individuals from November 2022 to April 2023 at 10 selected health facilities in Addis Ababa, Ethiopia. We enrolled the participants consecutively upon their arrival at health facilities until the required sample size was achieved. We used a structured questionnaire to collect data on the demographic and clinical characteristics of the participants. We also collected 3–5 ml of blood samples from all participants and tested for anti-Spike (anti-S) and anti-nucleocapsid (anti-N) antibodies using Cobas 6000. We utilized frequency, mean, or median to describe the data, the Mann-Whitney U test to compare groups, and a generalized linear regression model to assess factors associated with anti-S antibody concentration. We analyzed the data with SPSS version 26, and the level of significance was set at P-value < 0.05. Results: Of the naturally infected participants, 352 (99.5%) had anti-S antibodies and all (100%) had anti-N antibodies, whereas among vaccinated participants, all (100%) had anti-S antibodies, while 323 (91.6%) had anti-N antibodies. Anti-S antibodies produced by vaccinated individuals were significantly (P < 0.001) higher than those produced as a result of natural infection. Being young (P = 0.004), having hypertension (P < 0.001), and having diabetes (P < 0.001) were significantly associated with lower anti-S antibody levels, while being recently vaccinated and having a higher number of vaccine doses were significantly associated with higher anti-S antibody concentrations in vaccinated participants. Having diabetes (P < 0.001) were significantly associated with lower anti-S concentrations in participants who were naturally infected. Conclusion: There is a high seropositivity rate in both naturally infected and vaccinated individuals. However, vaccinated individuals had higher levels of SARS-CoV-2 antibodies than those who were naturally infected, which highlights the significant contribution of vaccination in increasing the protection of COVID-19 in Ethiopia. [ABSTRACT FROM AUTHOR]

Background: The high virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), has triggered global health and economic concerns. The absence of specific antiviral treatments and the side effects of repurposed drugs present persistent challenges. This study explored a promising antiviral herbal extract against SARS-CoV-2 from selected Thai medicinal plants based on in vitro efficacy and evaluated its antiviral lead compounds by molecular docking. Methods: Twenty-two different ethanolic-aqueous crude extracts (CEs) were rapidly screened for their potential activity against porcine epidemic diarrhea virus (PEDV) as a surrogate using a plaque reduction assay. Extracts achieving ≥ 70% anti-PEDV efficacy proceeded to the anti-SARS-CoV-2 activity test using a 50% tissue culture infectious dose method in Vero E6 cells. Molnupiravir and extract-free media served as positive and negative controls, respectively. Potent CEs underwent water/ethyl acetate fractionation to enhance antiviral efficacy, and the fractions were tested for anti-SARS-CoV-2 performance. The fraction with the highest antiviral potency was identified using liquid chromatography–high-resolution mass spectrometry (LC–HRMS). Molecular docking analyses of these compounds against the main protease (Mpro) of SARS-CoV-2 (6LU7) were performed to identify antiviral lead molecules. The top three hits were further evaluated for their conformational stability in the docked complex using molecular dynamics (MD) simulation. Results: The water fraction of mulberry (Morus alba Linn.) leaf CE (WF-MLCE) exhibited the most potent anti-SARS-CoV-2 efficacy with low cytotoxicity profile (CC50 of ~ 0.7 mg/mL), achieving 99.92% in pre-entry mode and 99.88% in postinfection treatment mode at 0.25 mg/mL. Flavonoids and conjugates were the predominant compounds identified in WF-MLCE. Molecular docking scores of several flavonoids against SARS-CoV-2 Mpro demonstrated their superior antiviral potency compared to molnupiravir. Remarkably, myricetin-3-O-β-D-galactopyranoside, maragrol B, and quercetin 3-O-robinobioside exhibited binding energies of ~ − 9 kcal/mol. The stability of each ligand–protein complex of these compounds with the Mpro system showed stability during MD simulation. These three molecules were pronounced as antiviral leads of WF-MLCE. Given the low cytotoxicity and high antiviral potency of WF-MLCE, it holds promise as a candidate for future therapeutic development for COVID-19 treatment, especially considering its economic and pharmacological advantages. [ABSTRACT FROM AUTHOR]

The pandemic caused by COVID-19 hinders everything on earth, including physical and mental health, daily life and the global economy. Currently, there are no defined drugs and few vaccines available on the market to combat SARS-CoV-2. A number of organic compounds have been designed and tested against the virus, but they have not shown promising activities. N -heterocycles, which are abundant in nature, is a significant source of pharmacologically active compounds. N -heterocycles have the potential to exert Anti- SARS-CoV-2 activity via various antiviral mechanisms, and some of them, have already used in clinics or under clinical evaluations for the processing of COVID-19. Therefore, N -heterocycles occupies an important position in the discovery of novel anti-SARS-CoV-2 agents. The current study is an effort to collect information's covering the articles published from 2019 to the beginning of this year 2022, regarding the recent development of N -heterocycles derivatives; indazole, triazolopyrimidine, pyrazolopyrimidine, quinoxaline, benzimidazole, benzodiazepine, indole, and quinoline, as potential anti-SARS-CoV-2 agents, their structure-activity relationship and mechanisms of action. [Display omitted] • The articles published from 2019 to 2022 about the anti-SARS-CoV-2 activity of some N-heterocyclic compounds. • The potential anti-SARS-CoV-2 of N-heterocycles derivatives. • N-heterocycles derivatives have demonstrated significant potential for drug development due to their high compatibility and versatility. • N-heterocyclic compounds have shown promising results in inhibiting the growth of SARS-CoV-2 cells. [ABSTRACT FROM AUTHOR]

The emergence of the severe acute respiratory syndrome 2 (SARS-CoV-2) as a global threat has driven the urgent need for the identification of bioactive molecules capable of controlling or completely eradicating this virus. Our group has been investigating isatin hybrids that block the binding of the human angiotensin-converting enzyme 2 (ACE2) and the viral spike protein. This work describes the synthesis and biological evaluation of two derivatives of isatin (indol-2,3-dione) based on a computational approach. Isatin, a secondary metabolite of tryptophan, has been used as the core structure and is a versatile and favorable precursor and as a privileged scaffold against this enzyme complex. The new compound scaffolds AVS-01 and AVS-02 were designed by modifications at the C-3 and N-1 positions, respectively, according to the various reagents available in our lab. Molecular docking of the designed compounds was used to explore their interactions with the target protein complex. The two designed compound scaffolds shown in this article showed quite distinct docking glide scores (GScore = −3.657 and −4.534 for AVS-01 and AVS-02, respectively). Several analogs were synthesized and tested in the quest to find a plausible scaffold for further synthesis. While compound AVS-02 showed inhibition of spike/ACE2 binding with an IC50 value of 8.8 µM, the reference compound hopeaphenol inhibited the interaction with an IC50 of 0.3 µM. Compound AVS-01 rather showed no inhibition of the SARS-CoV-2 spike/host ACE2 interaction with an IC50 > 32 µM. An estimation of their binding free energy (ΔGbind), and free energy of solvation (ΔGsolv) MM-GBSA calculations was carried out to re-evaluate the affinity to the target protein to gain further insights into the observed activity and non-activity. MM-GBSA calculation showed that ΔGbind = −35.91 kcal/mol and-25.32 kcal/mol for AVS-01 and AVS-02, respectively, and ΔGsolv = 25.56 kcal/mol and 16.92 kcal/mol for AVS-01 and AVS-02, respectively. This leads to the conclusion that the N-1 position of the indole-2,3-dione moiety favors the blockage of SARS-CoV-2 spike/ACE2 interactions compared to the C-3 position. Analysis of GScores, per-residue interaction energies, and free energies of binding and solvation showed that van der Waals interactions should favor the binding towards the spike/ACE2 complex.

In the global threat of SARS-CoV-2, individuals undergoing maintenance dialysis represent a vulnerable population with an increased risk of severe COVID-19 outcomes. Therefore, immunization against SARS-CoV-2 is an essential component of healthcare strategy for these patients. Existing data indicate that they tend to exhibit a reduced immune response to vaccines compared to the general population. Our study aimed to assess both humoral and cellular immune responses following two doses of an anti-SARS-CoV-2 mRNA vaccine, an ability to maintain adequate antibody titers over time, and potential relations with vitamin D, comorbidities and other factors in hemodialysis patients based on a single center experience. A total of 41/45 patients (91.1%) responded to the second dose of the anti-SARS-CoV-2 mRNA vaccine. The titer of anti-SARS-CoV-2 IgG class antibodies and levels of T cells three to four weeks after vaccination were lower in dialysis patients than in healthy controls. Antibodies titer in dialysis patients had a positive correlation with B lymphocytes and was related to cardiovascular diseases. The level of CD4+ cells had a negative correlation with hemodialysis vintage, as did the vitamin D level with post-vaccination seroconversion and decline in anti-SARS-CoV-2 antibodies titer during six months after vaccination. Hemodialysis patients had decreased amounts of CD4+ and CD8+ cells and lower levels of anti-SARS-CoV-2 antibodies than healthy controls. Therefore, chronic hemodialysis could lead to diminished cellular immunity and humoral immune response to the anti-SARS-CoV-2 mRNA vaccination and reduced protection from COVID-19. Comorbidity in cardiovascular diseases was associated with a lower level of specific anti-SARS-CoV-2 antibody titer. Vitamin D may be important in maintaining stable levels of anti-SARS-CoV-2 antibodies, while the duration of dialysis treatment could be one of the factors decreasing anti-SARS-CoV-2 antibody titer and determining lower CD4+ cell counts. [ABSTRACT FROM AUTHOR]

This study explores the potential anti-SARS-CoV-2 effects of gossypol (GP) and its AT-101 derivative through in silico molecular docking simulations. GP and AT-101 are natural and modified compounds, respectively, with promising biological activities. Using Autodock Vina software, molecular docking simulations were performed to assess the binding interactions between GP, AT-101, and the receptor binding domain of angiotensin-converting enzyme 2 (ACE2) which plays a vital role in facilitating viral entry into host cells. The docking results revealed that GP and AT-101 exhibited favorable interactions with ACE2, suggesting their potential as anti-SARS-CoV-2 agents. GP formed seven hydrogen bonds with ACE2, while AT101 formed eight, indicating more stable binding and superior interaction. However, it is important to acknowledge that these findings are based on in silico modeling and further research is required to validate the antiviral properties of l and AT-101 in vitro and in vivo. Moreover, the long-term safety and efficacy of these compounds for COVID-19 treatment warrant further investigation through clinical trials. In conclusion, this in silico study provides preliminary evidence of the potential antiSARS-CoV-2 effects of GP and AT-101 by demonstrating their ability to interact with ACE2. However, it is important to acknowledge that these findings are based on in silico modeling and further research is required to validate the antiviral properties of GP and AT-101 in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The pandemic novel coronavirus disease 2019 (COVID-19) has resulted in enormous economic damage and an exclusive health crisis, so developing a cure for this respiratory infectious disease has proceeded forward at full speed. Natural products and herbal medicines with accepted safety profiles are considered promising sources for discovering new medication leads. Genus Marrubium was reported to exhibit potential antiviral and antioxidant activities. Thus, this study aims to evaluate the inhibitory activity of the total methanolic extract and its soluble fractions: (petroleum ether, methylene chloride, and ethyl acetate) of the aerial parts of Marrubium alysson L. against SARSCoV-2 main protease (Mpro). Also, they were quantitatively assayed for their phenolics and flavonoids contents, in addition to evaluating their antioxidant activity. The results showed that the petroleum ether fraction has the highest inhibitory activity against SARS-CoV-2 main protease (Mpro) enzyme with IC50 value of 3.959±0.17 µg/mL compared to the reference tipranavir (IC50 1.89±0.08 µg/mL). The ethyl acetate fraction showed the highest total phenolics and flavonoids contents as well as the highest antioxidant activity (IC50 33.81±0.15 µg/mL) compared to the reference L-ascorbic acid (IC50 30.43±0.14 µg/mL). It could be concluded that soluble fractions of the total methanolic extract of Marrubium alysson L. may be used as an alternative source for developing new natural inhibitors against the main protease enzyme and may be suggested for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Background and Objectives: The efficacy of COVID‐19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas‐19 clinical trial showed that CP reduces the risk of progression to severe COVID‐19 at 28 days. Here, we aim to study ConPlas‐19 donors and characteristics that associate with high anti‐SARS‐CoV‐2 antibody levels. Materials and Methods: Four‐hundred donors were enrolled in ConPlas‐19. The presence and titres of anti‐SARS‐CoV‐2 antibodies were evaluated by EUROIMMUN anti‐SARS‐CoV‐2 S1 IgG ELISA. Results: A majority of 80.3% of ConPlas‐19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti‐SARS‐CoV‐2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24–3.42), with more than 7 days of COVID‐19 symptoms (RR 1.89; 95% CI 1.05–3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16–5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91–3.06). Conclusion: SARS‐CoV‐2 CP candidate donors' age, duration of COVID‐19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID‐19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks. [ABSTRACT FROM AUTHOR]

Marine algal extracts exhibit a potent inhibitory effect against several enveloped and non-enveloped viruses. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several adverse effects, including an increased mortality rate. The anti-COVID-19 agents are still limited; this issue requires exploring novel, effective anti-SARS-CoV-2 therapeutic approaches. This study investigated the antiviral activity of an aqueous extract of Ulva lactuca, which was collected from the Gulf of Suez, Egypt. The aqueous extract of Ulva lactuca was characterized by high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Energy Dispersive X-ray (EDX) analyses. According to the HPLC analysis, the extract comprises several sugars, mostly rhamnose (32.88%). The FTIR spectra showed numerous bands related to the functional groups. EDX analysis confirmed the presence of different elements, such as oxygen (O), carbon (C), sulfur (S), magnesium (Mg), potassium (K), calcium (Ca), and sodium (Na), with different concentrations. The aqueous extract of U. lactuca (0.0312 mg/mL) exhibited potent anti-SARS-CoV-2 activity via virucidal activity, inhibition of viral replication, and interference with viral adsorption (% inhibitions of 64%, 33.3%, and 31.1%, respectively). Consequently, ulvan could be a promising compound for preclinical study in the drug development process to combat SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Context: When the epidemic first broke out, no specific treatment was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The urgent need to end this unusual situation has resulted in many attempts to deal with SARS-CoV-2. In addition to several types of vaccinations that have been created, anti-SARS-CoV-2 monoclonal antibodies (mAbs) have added a new dimension to preventative and treatment efforts. This therapy also helps prevent severe symptoms for those at a high risk. Therefore, this is one of the most promising treatments for mild to moderate SARS-CoV-2 cases. However, the availability of anti-SARS-CoV-2 mAb therapy is limited and leads to two main challenges. The first is the privacy challenge of selecting eligible patients from the distribution hospital networking, which requires data sharing, and the second is the prioritization of all eligible patients amongst the distribution hospitals according to dose availability. To our knowledge, no research combined the federated fundamental approach with multicriteria decision-making methods for the treatment of SARS-COV-2, indicating a research gap. Objective: This paper presents a unique sequence processing methodology that distributes anti-SARS-CoV-2 mAbs to eligible high-risk patients with SARS-CoV-2 based on medical requirements by using a novel federated decision-making distributor. Method: This paper proposes a novel federated decision-making distributor (FDMD) of anti-SARS-CoV-2 mAbs for eligible high-risk patients. FDMD is implemented on augmented data of 49,152 cases of patients with SARS-CoV-2 with mild and moderate symptoms. For proof of concept, three hospitals with 16 patients each are enrolled. The proposed FDMD is constructed from the two sides of claim sequencing: central federated server (CFS) and local machine (LM). The CFS includes five sequential phases synchronised with the LMs, namely, the preliminary criteria setting phase that determines the high-risk criteria, calculates their weights using the newly formulated interval-valued spherical fuzzy and hesitant 2-tuple fuzzy-weighted zero-inconsistency (IVSH2-FWZIC), and allocates their values. The subsequent phases are federation, dose availability confirmation, global prioritization of eligible patients and alerting the hospitals with the patients most eligible for receiving the anti-SARS-CoV-2 mAbs according to dose availability. The LM independently performs all local prioritization processes without sharing patients' data using the provided criteria settings and federated parameters from the CFS via the proposed Federated TOPSIS (F-TOPSIS). The sequential processing steps are coherently performed at both sides. Results and Discussion: (1) The proposed FDMD efficiently and independently identifies the high-risk patients most eligible for receiving anti-SARS-CoV-2 mAbs at each local distribution hospital. The final decision at the CFS relies on the indexed patients' score and dose availability without sharing the patients' data. (2) The IVSH2-FWZIC effectively weighs the high-risk criteria of patients with SARS-CoV-2. (3) The local and global prioritization ranks of the F-TOPSIS for eligible patients are subjected to a systematic ranking validated by high correlation results across nine scenarios by altering the weights of the criteria. (4) A comparative analysis of the experimental results with a prior study confirms the effectiveness of the proposed FDMD. Conclusion: The proposed FDMD has the benefits of centrally distributing anti-SARS-CoV-2 mAbs to high-risk patients prioritized based on their eligibility and dose availability, and simultaneously protecting their privacy and offering an effective cure to prevent progression to severe SARS-CoV-2 hospitalization or death. [ABSTRACT FROM AUTHOR]

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a–3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a–g) were assessed in Vero E6 cells via MTT assay to calculate the CC50 and inhibitory concentration 50 (IC50) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with an IC50 value of 0.73 μg/mL. Moreover, F3e was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure–activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity. Emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a–3g). The most potent 3e-loaded EMLs (F3e) showed an IC50 value of 0.73 μg/mL against SARS-CoV-2. F3e exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Molecular docking, molecular dynamics (MD) simulations, and MM-GBSA calculations were performed. Structure–activity relationship (SAR) study was discussed to study the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide on the anti-SARS-CoV-2 activity. [ABSTRACT FROM AUTHOR]

The current coronavirus disease 2019 (COVID-19) outbreak, caused by the infection of SARS-CoV-2, seems to be a tough global challenge because of its highly contagious nature and rapid evolution of the virus strain. As no effective clinical drugs are available for the treatment of this disease in the early phase till to date, scientists are hunting for drugs from natural sources for its treatment. Quercetin, a dietary polyphenolic flavonoid found in fruits and vegetables, has been reported to exhibit various health-benefit pharmacological properties including antioxidant, anti-inflammatory, antimicrobial, antiviral and anticancer properties. In silico and in vitro studies demonstrated that quercetin potently inhibits the infections of SARS-CoV-2 and other coronaviruses by interfering with viral entry and replication via inhibiting the activity of host ACE2 receptor, and viral S-, 3CL-, PL-, RdRp- and Nsp13 - proteases. Moreover, quercetin is able to suppress oxidative stress, cytokine storm, thrombosis, sepsis and lung fibrosis, and thereby very likely is able to mitigate COVID-19 infection. In this review article, we elaborately discussed the antiviral, immunomodulatory, antioxidant properties of quercetin against viral infections and other diseases, as well as on its nanoformulations for enhancement of oral bioavailability and clinical efficacy in COVID-19 infection for its development as clinical drug for COVID-19.

Background and purpose: Rapid detection test via lateral flow immunoassay (LFIA) is employed as an alternate method to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Gold nanoparticles (AuNPs), a vital component of LFIA, can be synthesized by laser ablation technique. This intense laser radiation may result in monodisperse gold nanoclusters, which are impurity-free and demonstrate innovative biocompatible surface chemistry. In this current research, laser-ablated AuNPs are produced and coupled with an anti-spike SARS-CoV-2 monoclonal antibody (mAb) generated in our prior study. Experimental approach: The AuNPs from 30,000 shots of laser ablation exhibited a robust red color with a maximum absorbance peak at 520 nm. The performance of AuNPs-mAb conjugates as a signal reporter was then evaluated in half-stick LFIA. Key results: The size distribution of AuNPs shows a relatively monodisperse and unimodal distribution with average particle diameters of 44.77 nm and a surface potential of -38.5 mV. The purified anti-spike mAb SARS-CoV-2 yielded two protein bands, representing the mAb heavy chain at 55 kDa and its light chain at 25 kDa. The immobilization of anti-spike mAb onto the surface of AuNPs revealed that 25 g/ml of mAb at phosphate buffer pH 9 was required to stabilize the AuNPs. The functional test of this conjugate was performed using dipstick LFIA, and the result shows that the AuNPs-mAb conjugates could successfully detect commercial spike antigen of SARS-CoV-2 at 10 ng level. Conclusion: In this study, laser-ablated AuNPs were functionalized with anti-spike mAb SARS-CoV-2 and successfully used as a signal reporter in half-stick LFIA for detecting antigen spike SARS-CoV-2.

In this article, emulsomes (EMLs) were fabricated to encapsulate the N-(5-nitrothiazol-2-yl)-carboxamido derivatives (3a–3g) in an attempt to improve their biological availability and antiviral activity. Next, both cytotoxicity and anti-SARS-CoV-2 activities of the examined compounds loaded EMLs (F3a–g) were assessed in Vero E6 cells via MTT assay to calculate the CC50 and inhibitory concentration 50 (IC50) values. The most potent 3e-loaded EMLs (F3e) elicited a selectivity index of 18 with an IC50 value of 0.73 μg/mL. Moreover, F3e was selected for further elucidation of a possible mode of action where the results showed that it exhibited a combination of virucidal (>90%), viral adsorption (>80%), and viral replication (>60%) inhibition. Besides, molecular docking and MD simulations towards the SARS-CoV-2 Mpro were performed. Finally, a structure–activity relationship (SAR) study focussed on studying the influence of altering the size, type, and flexibility of the α-substituent to the carboxamide in addition to compound contraction on SARS-CoV-2 activity.

In the global threat of SARS-CoV-2, individuals undergoing maintenance dialysis represent a vulnerable population with an increased risk of severe COVID-19 outcomes. Therefore, immunization against SARS-CoV-2 is an essential component of healthcare strategy for these patients. Existing data indicate that they tend to exhibit a reduced immune response to vaccines compared to the general population. Our study aimed to assess both humoral and cellular immune responses following two doses of an anti-SARS-CoV-2 mRNA vaccine, an ability to maintain adequate antibody titers over time, and potential relations with vitamin D, comorbidities and other factors in hemodialysis patients based on a single center experience. A total of 41/45 patients (91.1%) responded to the second dose of the anti-SARS-CoV-2 mRNA vaccine. The titer of anti-SARS-CoV-2 IgG class antibodies and levels of T cells three to four weeks after vaccination were lower in dialysis patients than in healthy controls. Antibodies titer in dialysis patients had a positive correlation with B lymphocytes and was related to cardiovascular diseases. The level of CD4+ cells had a negative correlation with hemodialysis vintage, as did the vitamin D level with post-vaccination seroconversion and decline in anti-SARS-CoV-2 antibodies titer during six months after vaccination. Hemodialysis patients had decreased amounts of CD4+ and CD8+ cells and lower levels of anti-SARS-CoV-2 antibodies than healthy controls. Therefore, chronic hemodialysis could lead to diminished cellular immunity and humoral immune response to the anti-SARS-CoV-2 mRNA vaccination and reduced protection from COVID-19. Comorbidity in cardiovascular diseases was associated with a lower level of specific anti-SARS-CoV-2 antibody titer. Vitamin D may be important in maintaining stable levels of anti-SARS-CoV-2 antibodies, while the duration of dialysis treatment could be one of the factors decreasing anti-SARS-CoV-2 antibody titer and determining lower CD4+ cell counts.

This study aimed to investigate the phytochemical composition and biological activity of Salsola tetragona Delile. (Amaranthaceae), a medicinal plant. The study evaluated the antioxidant potential of the crude extract and five fractions of S. tetragona using DPPH•, ABTS•+, CUPRAC, and metal chelating assays. The anti-inflammatory activity was determined using a protein denaturation assay, and the antibacterial activity was determined by the Minimum inhibitory concentrations (MICs) for the growth of Escherichia coli and Staphylococcus aureus strains. The MTT test and an in vitro scratch assay evaluated the effects on cell viability and cell migration. The potential anti-SARS-CoV-2 activity was assessed by analyzing the effects on the interaction between ACE2 and Spike protein. The bioactive compounds present in the plant were identified using LC-HR/MS analysis. The crude hydromethanolic extract (STM) and five fractions of S. tetragona, n-hexane (STH), dichloromethane (STD), ethyl acetate (STE), n-butanol (STB), and aqueous (STW) showed significant antioxidant activity in four different tests. In the anti-inflammatory assay, the ethyl acetate fraction exhibited significantly higher activity than Aspirin® (IC50 = 13 ± 5 µg/mL). The crude extract and its fractions showed positive antibacterial activity with similar MICs. In the cytotoxicity assay against the breast cancer cell line MCF7, the dichloromethane fractions (STD) were very effective and demonstrated superiority over the other fractions (IC50 = 98 µg/mL). Moreover, the potential of the extract and fractions as anti-SARS-CoV-2, the ethyl acetate, and dichloromethane fractions demonstrated important activity in this test. LC-HR/MS analysis identified 16 different phenolic compounds, Eleven of which had not been previously reported in the genus Salsola. The results suggest that the extracts of S. tetragona have the potential to become new sources for developing plant-based therapies for managing a range of diseases.

To effectively respond to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), an increasing number of researchers are focusing on the antiviral activity of cepharanthine (CEP), which is a clinically approved drug being used for over 70 years. This review aims to provide a brief overview of CEP and summarize its recent findings in quantitative analysis, pharmacokinetics, therapeutic potential, and mechanism in antiviral and anti-SARS-CoV-2 activity. Given its remarkable capacity against SARS-CoV-2 infection in vitro and in vivo, with its primary target organ being the lungs, and its good pharmacokinetic profile; mature and stable manufacturing technique; and its advantages of safety, effectiveness, and accessibility, CEP has become a promising drug candidate for treating COVID-19 despite being an old drug. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a highly contagious and pathogenic virus that first appeared in late December 2019 and caused a global pandemic in a short period. The virus is a single-stranded RNA virus belonging to the Coronaviridae family. Numerous treatments have been developed and tested in response to the pandemic, particularly antiviral drugs. Among them, GS441524 (GS441), a nucleoside antiviral drug, has demonstrated promising results in inhibiting SARS-CoV-2. Nevertheless, the limited oral bioavailability of GS441 restricts its application to patients with the virus. In this study, a novel prodrug of GS441 (NGP-1) with an isobutyl ester and cyclic carbonate structure was designed and synthesized. Its purity and the stability in different artificial digestive juices of NGP-1 was determined with HPLC-DAD methods. The pharmacokinetics of NGP-1 and GS441 were studied in rats via gavage administration. A new LC-MS/MS method was developed to quantitatively analyze GS441 in plasma samples. The results showed that the ka, Cmax, and MRT of converted GS441 from NGP-1 were 5.9, 3, and 2.5 times greater than those of GS441 alone. The Frel of NGP-1 was approximately four-fold that of GS441, with an AUC0–∞ of 9716.3 h·ng mL−1. As a prodrug of GS441, NGP-1 increased its lipophilicity, absorption, and bioavailability, indicating that it holds promise in improving the clinical efficacy of anti-SARS-CoV-2 medications. [ABSTRACT FROM AUTHOR]

A series of novel nickel (II) complexes [Ni(L¹)](1), [Ni(L²)](2), [Ni(L³)](3) and [Ni(L4)](4) of salen-type Schiff base ligands (L¹H2-L4H2), have been designed and synthesized, and their interaction with SARS-CoV-2 for COVID-19 and HIV virus were studied by molecular docking methods for possible therapeutic drug candidates as anti-COVID-19 and anti-HIV agents. The salen-type Schiff base ligands were condensation products of ethylene diamine with related aldehydes (3,5-Dichlorosalicylaldehyde, 5-Bromo-3-methoxy-2-hydroxy-benzaldehyde, 3,5-Diiodosalicylaldehyde, 3,5-Dinitrosalicylaldehyde). They were coordinated to metal ions through the tetradentate-N2O2 donor atoms. The newly synthesized complexes were fully characterized by different spectroscopic and physicochemical methods. The molecular and electronic structures of the complexes are studied by DFT based quantum chemical calculations. Additionally, inspired from recent developments to find inhibitors of the SARS-CoV-2 main protease, molecular docking studies are performed on the complexes to predict the binding mode and interactions between the ligands and the main protease of the SARS-CoV-2 (PDB ID: 7O46) for COVID-19. Also the binding potential of the nickel(II) complexes with HIV virus (PDB ID: 1UUI) are studied using in-silico molecular docking approach. The X-ray crystallographic structure of the main protease of the SARS-CoV-2 and HIV virus are retrieved from the protein data bank and used as receptor proteins. The molecular docking calculations of the nickel (II) complexes (1)-(4) with SARS-CoV-2 (PDB ID: 7O46) virus revealed the higher binding energy (-9.6 to -6.9 kcal/mol) than that of HIV virus (-9.3 to -6.7 kcal/mol) as well as docking results of chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) as anti-SARS-CoV-2 drugs. Overall, in-silico molecular docking study offers the potential role of the nickel (II) complexes as anti-COVID-19 and anti-HIV agents. [ABSTRACT FROM AUTHOR]

Objective: The current study investigated the immune response of maternal coronavirus disease 2019 (COVID‐19) vaccination and vertical transmission of anti–severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike (S) and nucleocapsid (N) proteins. Study design: This retrospective study included pregnant women in Bahrain Defense Force Hospital from March 2021 to September 2021 who were vaccinated with Sinopharm or Pfizer/BioNTech. Testing of anti‐N and ‐S levels from paired samples of maternal and umbilical cord blood was performed at the time of delivery. The immune response to vaccination, association with maternal and fetal factors, and vertical transmission of antibodies were studied. Results: The current study included 79 pregnant women. The median gestational age for those vaccinated with Sinopharm was 28 weeks and those vaccinated with Pfizer was 31 weeks, with 100% of the vaccinated population generating antibodies and showing vertical transmission. The anti‐N and ‐S titers and interval frequencies varied in both vaccinations. The anti‐N and ‐S and transfer ratio statistically correlated with maternal age, gestational age at delivery, latency period, and birth weight of the neonates differently in both vaccines. In addition, the peak level of antibodies and transfer ratios varied. Conclusion: Although variations are exhibited in both types of vaccination, the vaccinated pregnant population generated a significant level of anti‐N and ‐S and showed vertical transmission. Synopsis: Although variations are exhibited in the type of COVID‐19 vaccination, the vaccinated pregnant population generated a significant level of anti‐N and ‐S and showed vertical transmission. [ABSTRACT FROM AUTHOR]

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has opened the door to potential threats of the respiratory system. The discovery of drugs from natural sources is one of the most important strategies for treating the upper respiratory tract. In this study, we investigated the selected formulated EOs activities against Gram-negative (E. coli, K. pneumonia, and P. aeruginosa) and Gram-positive (S. aureus, E. fecalis) bacteria and against the SARS-CoV-2 virus, with the mode of action investigated as anti-SARS-CoV-2. Cinnamomum zeylanicum and Syzygium aromaticum EOs were the most promising antibacterial oils. C. zeylanicum EO showed MIC values of 1, 1, 2, ≤0.5, and 8 µg/mL against E. coli, K. pneumoniae, P. aeruginosa, S. aureus, and E. fecalis, respectively, while S. aromaticum EO showed MIC values of 8, 4, 32, 8, 32 µg/mL against the same organisms. The cytotoxic activity of the oil samples was tested in VERO-E6 cells using (MTT) assay and showed that the safest oil was F. vulgare, then L. nobilis, C. carvi, S. aromaticum, and E. globulus. The most potent antiviral EOs were C. zeylanicum oil and S. aromaticum, with IC50 value of 15.16 and 96.5 µg/mL, respectively. Moreover, the safety index of S. aromaticum EO (26.3) was greater than the oil of C. zeylanicum (7.25). The mechanism by which C. zeylanicum oil exerts its antiviral activity may involve both the virucidal effect and its impact on viral reproduction. The nano-emulsion dosage form of the potent EOs was prepared and re-examined against the same bacterial and viral strains. Finally, the chemical characterization of these promising essential oils was analyzed and identified using the GC–MS approach. To the best of our knowledge, this is the first report concerning the in vitro investigation of anti-SARS-CoV-2 activity of these selected essential oils, along with a proposed mechanism for the potent oil's activity.

Marine algal extracts exhibit a potent inhibitory effect against several enveloped and non-enveloped viruses. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several adverse effects, including an increased mortality rate. The anti-COVID-19 agents are still limited; this issue requires exploring novel, effective anti-SARS-CoV-2 therapeutic approaches. This study investigated the antiviral activity of an aqueous extract of Ulva lactuca, which was collected from the Gulf of Suez, Egypt. The aqueous extract of Ulva lactuca was characterized by high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Energy Dispersive X-ray (EDX) analyses. According to the HPLC analysis, the extract comprises several sugars, mostly rhamnose (32.88%). The FTIR spectra showed numerous bands related to the functional groups. EDX analysis confirmed the presence of different elements, such as oxygen (O), carbon (C), sulfur (S), magnesium (Mg), potassium (K), calcium (Ca), and sodium (Na), with different concentrations. The aqueous extract of U. lactuca (0.0312 mg/mL) exhibited potent anti-SARS-CoV-2 activity via virucidal activity, inhibition of viral replication, and interference with viral adsorption (% inhibitions of 64%, 33.3%, and 31.1%, respectively). Consequently, ulvan could be a promising compound for preclinical study in the drug development process to combat SARS-CoV-2.

Objective. To describe the humoral response in a cohort with mild and asymptomatic SARS-CoV-2 infection previ­ously identified in a community-based serological survey. Materials and methods. This study was an observational follow up of 193 subjects previously identified with positive anti-SARS-CoV-2 antibodies invited for a second test 112 days after the first sampling. All completed a standardized electronic questionnaire. IgM/IgG antibodies were determined using a qualitative IgM/IgG chemiluminescent immunoassay. Results. Among the 193 eligible subjects, a total of 174 (90%) attended the follow-up visit, and their serum samples were tested. Of the samples, 171 (98.3%) were still positive, and 3 (1.7%) were negative. Also, the cut-off index (COI) value of the immunoassay significantly increased from the first to the second test (P

Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious disease caused by SARS-CoV-2. Inflammatory factors may play essential roles in COVID-19 progression. Huashi Baidu Decoction (HSBD) is a traditional Chinese medicine (TCM) formula that can expel cold, dispel dampness, and reduce inflammation. HSBD has been widely used for the treatment of COVID-19. However, the active ingredients and potential targets for HSBD to exert anti-inflammatory or anti-SARS-CoV-2 effects remain unclear. In this paper, the active ingredients with anti-inflammatory or anti-viral effects in HSBD and their potential targets were screened using the Discovery Studio 2020 software. By overlapping the targets of HSBD and COVID-19, 8 common targets (FYN, SFTPD, P53, RBP4, IL1RN, TTR, SRPK1, and AKT1) were identified. We determined 2 key targets (P53 and AKT1) by network pharmacology. The main active ingredients in HSBD were evaluated using the key targets as receptor proteins for molecular docking. The results suggested that the best active ingredients Kaempferol2 and Kaempferol3 have the potential as supplements for the treatment of COVID-19.

A theoretical and experimental approach for a series of synthetic aromatic organic compounds as salicylaldehyde thiosemicarbazones were prepared from 4,4-dimethyl-3-thiosemicarbazide and substituted salicylaldehydes. The newly synthesized compounds were fully characterized by FT-IR, UV-vis, 1H-NMR, 13C-NMR, CHNS, HRMS, and fluorescence spectroscopy. DFT calculations were performed on the compounds to get a structure-property relationship. Some global reactivity descriptors like chemical potential (μ), electronegativity (χ), hardness (η), and electrophilicity index (ω) were also evaluated using DFT method. Optical nonlinearity response of our novel compounds was also studied which may be significant for the hi-tech NLO applications. These compounds were also evaluated for their antibacterial activities against certain strains of Gram-positive and Gram-negative bacteria. They displayed moderate activity against using bacterial strains. Additionally, inspiring from recent developments to find a potential inhibitor for COVID-19 virus, molecular docking calculations were also performed on studied compounds to see if our novel compounds show affinity for main protease (Mpro) of SARS-CoV-2 (PDB ID: 6LU7). We have found stable docked structures where docked compounds could readily bound to the SARS-CoV-2, which would be lethal to main protease (Mpro). The molecular docking calculations of the present compounds into the protease of SARS-CoV-2 virus revealed the binding energy in the range of −7.86 to 9.92 kcal/mol with inhibition constant values in the range of 1.360–5.820 µM. These binding affinities are reasonably well as compared to recently docking results of anti-SARS-CoV-2 drugs like chloroquine (−6.293 kcal/mol), hydroxychloroquine (−5.573 kcal/mol) and remdesivir (−6.352 kcal/mol) when targeted to the active-site of SARS-CoV-2 main protease (Mpro). [ABSTRACT FROM AUTHOR]

The high nutritional value and diverse functional properties of egg yolk proteins have led to its widespread use in the fields of food, medicine, and cosmetics. Various extraction methods have been reported to obtain the proteins from egg yolk, however, their utilization is limited due to the relatively low extraction efficiency and/or toxic solvents involved. Several simpler and greener technologies, especially physical fields (ultrasound), have been successfully developed to improve the extraction efficiency. The egg yolk proteins may exert multiple biological activities, enabling them to be a promising tool in improve human health and wellbeing, such as anti-obesity, anti-atherosclerosis, anti-osteoporosis, diagnosis and therapy for SARS-CoV-2 infections. This article summarizes the novel extraction technologies and latest applications of the egg yolk proteins in the recent 5 years, which should stimulate their utilization as health-promoting functional ingredients in foods and other commercial products. [ABSTRACT FROM AUTHOR]

The prospective study was conducted to evaluate the prevalence of COVID-19 in kidney transplant patients in relation to their immune status after three doses of the BNT162b2 (Pfizer-BioNTech) vaccine during one post-pandemic year based on the experience of one center—Hospital of Lithuanian University of Health Sciences. Thirty-three patients were invited for a follow-up visit 3 to 6 weeks after anti-SARS-CoV-2 vaccination and were obliged to report having COVID-19 during the one-year post-pandemic period. Forty-two percent of patients developed antibody response against SARS-CoV-2 after the third dose of the vaccine. The number of COVID-19 cases during the post-pandemic period did not differ significantly between seropositive and seronegative patients. However, only seronegative patients were hospitalized due to COVID-19. The anti-SARS-CoV-2 antibody titer in seropositive patients correlated with a relative number of CD3+ cells (R = 0.685, p = 0.029). The CD8+/CD38+ ratio in this group increased 2-fold after the anti-SARS-CoV-2 vaccination. Higher antibody response to the COVID-19 vaccine was associated with better kidney function. The anti-SARS-CoV-2 antibody titer relation with the components of cellular immunity (CD3+ cells and CD8+/CD38+ ratio) shows a role of both chains during the response to the anti-SARS-CoV-2 vaccine in kidney transplant patients. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 as a zoonotic virus has significantly affected daily life and social behavior since its outbreak in late 2019. The concerns over its transmission through different media directly or indirectly have evoked great attention about the survival of SARS-CoV-2 virions in the environment and its potential infection of other animals. To evaluate the risk of infection by SARS-CoV-2 and to counteract the COVID-19 disease, extensive studies have been performed to understand SARS-CoV-2 biogenesis and its pathogenesis. This review mainly focuses on the molecular architecture of SARS-CoV-2, its potential for infecting marine animals, and the prospect of drug discovery using marine natural products to combat SARS-CoV-2. The main purposes of this review are to piece together progress in SARS-CoV-2 functional genomic studies and antiviral drug development, and to raise our awareness of marine animal safety on exposure to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Introduction: A global vaccination program was implemented in late 2020 to end the pandemic caused by the SARS-CoV-2 virus. However, the immune response elicited by the vaccines proved to be insufficient due to the rapid emergence of new viral mutations. Therefore, the factors influencing cellular and humoral immune responses after the administration of different vaccines against SARS-CoV2 need to be identified. Materials: In the present study, anti-SARS-CoV-2 antibody titers were analyzed 20 to 50 days after the administration of a third (booster) dose of the BNT162b2 vaccine in 192 residents of the city of Olsztyn (Poland) primed with two AstraZeneca or Pfizer/BioNTech vaccines. Methods: Antibody titers were determined in venous blood serum in the ECLIA test using the Cobas e411 Roche analyzer. Results: The study revealed that persons who received three doses of the Pfizer/BioNTech vaccine had significantly higher antibody titers than those who received two doses of AstraZeneca and a booster dose of Pfizer/BioNTech. [ABSTRACT FROM AUTHOR]

Based on the simplicity and modification of the medication osimertinib, two new series of indolyle-pyrimidine-5-carbonitrile scaffolds were created and synthesized with dual action as anti-SARS-Cov-2 and anticancer. The newly created heterocyclic compounds' chemical structures were effectively characterized. With IC50 values of 18.52, 20.89, and 19.85, respectively, compounds 9b, 10 , and 15 had inhibitory actions against SARS-CoV-2 when compared to remdesivir and chloroquine, which served as pharmacological controls and had IC50 values of 3.38 μM and 24.9 μM, respectively. Furthermore, compounds 9a and 13 showed anti-proliferative activity against HepG2 cell lines with IC 50s of 5.63 μM and 3.06 μM, respectively, in comparison to doxorubicin's IC 50 of 7.4 μM. qRT-PCR revealed that HepG2 cells treated with compounds 9a and 13 showed increased p53 expression levels and decreased CDK1 and PI3K expression levels in comparison to doxorubicin. Molecular dynamics simulations of 20 ns duration were performed with PI3Kα, PI3Kγ, and CDK and active compound complexes. The results confirm that compound 13 has the potential to be a therapeutic candidate for additional preclinical and clinical research, as indicated by the molecular docking data. Promising candidate compound 13 to interact with the target receptor cyclin‑dependent kinase 1 (CDK1). [Display omitted] • Two new series of indolyle-pyrimidine-5-carbonitrile scaffolds were designed and synthesized with dual activity as anticancer and anti-SARS-Cov-2 based on the modification and simplification of the osimertinib drug. • Compounds 9b , 10 , and 15 showed inhibitory effects against SARS-CoV-2 with IC 50 18.52, 20.89, and 19.85. • Compounds 9a and 13 showed anti-proliferative activity against HepG2 cell lines with IC 50 s of 5.63 μM and 3.06 μM, respectively. • Compounds 13 and 9a elicit the induction of apoptosis in HepG2 cells by increasing the expression level of p53 gene and decreasing the expression level of PI3K and CDK1 genes. • Compound 13 showed stable binding interactions with PI3Kα, PI3Kγ, and CDK1 protein's active site, according to the binding results (PDB codes 4TV3 , 7JWE, 6GU7). [ABSTRACT FROM AUTHOR]

• Combination of CEP and Lut shows synergism without antagonism. • Ingestion of CEP before Lut is more conducive to the efficient utilization of drugs. • Inhibition mechanism of CEP and Lut on Pep is non-competitive. The antimicrobial, anticancer, and anti-SARS-CoV-2 activities of cepharanthine (CEP) combined with luteolin (Lut) were compared and analyzed by in vitro bioactivity experiment and molecular docking. CEP shows stronger biological activity than Lut, and their combination shows synergism without antagonism, especially in the fungal inhibition and anticancer activity experiments. It is believed that the antiviral activity is still effective confirmed by the simulation between two drugs and anti-SARS-CoV-2. Further, pepsin (Pep) was chosen for imitative gastroenteric environments to study its protease activity and structure effected by two drugs. The results show that the inhibitory mechanism of Lut/CEP is non-competitive inhibition, the binding mechanism is static quenching driven by enthalpy, the order of drug addition can affect the strength of binding ability, and the strength of binding ability is positively correlated with the inhibitory effect on enzyme activity. The ingestion of CEP before ingestion of Lut is more conducive to the efficient utilization of them. Their combination can not only decrease the dosage and toxicity, but also enhance the anti-inflammatory and anti-virus effects. These results can provide theoretical support for the development and utilization of Lut and CEP, and may supply one of the treatment for deal with the newly appeared viruses. [ABSTRACT FROM AUTHOR]

Natural products play an essential role in new drug discovery. In the present study, we determined the anti-SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2), antioxidant, antiplasmodial, and antimicrobial activities of Pterocarpus macrocarpus Kurz. heartwood and structurally characterized the bioactive compounds. P. macrocarpus Kurz. heartwood was macerated with n-hexane, ethyl acetate, and ethanol, respectively, for 7 days, three times. The compounds were isolated by recrystallization with n-hexane and evaluated by thin-layer chromatography (TLC), gas chromatography-mass spectrophotometry (GC-MS), Fourier transform infrared spectroscopy (FITR), and nuclear magnetic resonance (NMR) spectroscopy. Ethyl acetate, ethanol, n-hexane extracts, and homopterocarpin exhibited antiplasmodial activity at 1.78, 2.21, 7.11, and 0.52 μg/ml, respectively, against P. falciparum 3D7 with low toxicity (selectivity index/SI ≥ 28.46). GC-MS identified compound showed in silico anti-SARS-CoV-2 binding affinity with stigmasterol and SARS-CoV-2 helicase of −8.2 kcal/mol. Ethyl acetate extract exhibited the best antioxidant activity against DPPH (0.76 ± 0.92 μg/ml) and ABTS (0.61 ± 0.46 μg/ml). They also demonstrated antimicrobial activity against B. subtilis, ethanol and ethyl acetate extracts against E. coli and C. albicans, and ethanol extract against S. aureus with diameter zone of inhibition of more than 1 cm. The results highlighted antiplasmodial activity of extracts and homopterocarpin from P. macrocarpus Kurz. heartwood and its potent binding in silico to anti-SARS-CoV-2 proteins with low toxicity. This study also confirmed that extracts exhibited antioxidant and antimicrobial activities. Further studies are needed to assess the safety and clinical trial of P. macrocarpus Kurz. for development as new drug candidate.

IntroductionCoronavirus Disease-2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. Severe cases of COVID-19 are characterized by an intense inflammatory process that may ultimately lead to organ failure and patient death. Qingfei Paidu Decoction (QFPD), a traditional Chines e medicine (TCM) formula, is widely used in China as anti-SARS-CoV-2 and anti-inflammatory. However, the potential targets and mechanisms for QFPD to exert anti-SARS-CoV-2 or anti-inflammatory effects remain unclear.MethodsIn this study, Computer-Aided Drug Design was performed to identify the antiviral or anti-inflammatory components in QFPD and their targets using Discovery Studio 2020 software. We then investigated the mechanisms associated with QFPD for treating COVID-19 with the help of multiple network pharmacology approaches.Results and discussionBy overlapping the targets of QFPD and COVID-19, we discovered 8 common targets (RBP4, IL1RN, TTR, FYN, SFTPD, TP53, SRPK1, and AKT1) of 62 active components in QFPD. These may represent potential targets for QFPD to exert anti-SARS-CoV-2 or anti-inflammatory effects. The result showed that QFPD might have therapeutic effects on COVID-19 by regulating viral infection, immune and inflammation-related pathways. Our work will promote the development of new drugs for COVID-19.

The current outbreak of COVID-19 cases worldwide has been responsible for a significant number of deaths, especially in hospitalized patients suffering from comorbidities, such as obesity, diabetes, hypertension. The disease not only has prompted an interest in the pathophysiology, but also it has propelled a massive race to find new anti-SARS-CoV-2 drugs. In this scenario, known drugs commonly used to treat other diseases have been suggested as alternative or complementary therapeutics. Herein we propose the use of sitagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP4) used to treat type-II diabetes, as an agent to block and inhibit the activity of two proteases, 3CLpro and PLpro, related to the processing of SARS-CoV-2 structural proteins. Inhibition of these proteases may possibly reduce the viral load and infection on the host by hampering the synthesis of new viruses, thus promoting a better outcome. In silico assays consisting in the modeling of the ligand sitagliptin and evaluation of its capacity to interact with 3CLpro and PLpro through the prediction of the ligand bioactivity, molecular docking, overlapping of crystal structures, and molecular dynamic simulations were conducted. The experiments indicate that sitagliptin can interact and bind to both targets. However, this interaction seems to be stronger and more stable to 3CLpro (ΔG = −7.8 kcal mol−1), when compared to PLpro (ΔG = −7.5 kcal mol−1). This study suggests that sitagliptin may be suitable to treat COVID-19 patients, beyond its common use as an anti-diabetic medication. In vivo studies may further support this hypothesis. [ABSTRACT FROM AUTHOR]

(−)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans -fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections. [ABSTRACT FROM AUTHOR]

COVID-19 is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The herbal formula, Ping An Fang Yu Yin (PAFYY), has been used to prevent respiratory viral infections for many years. This study aims to evaluate the effect of PAFYY on SARS-CoV-2 infection, oxidative stress, and inflammation via in vitro, investigate the chemical composition by full constituent quantitative analysis, and verify its anti-viral potential against SARS-CoV-2 using in silico. In this study, a total of eleven compounds, twenty amino acids, saccharide compositions, and trace elements were found and quantitatively determined by chromatographic techniques. PAFYY displayed free radical scavenging activity (DPPH, SC50: 1.24 ± 0.09 mg/mL), SOD activity (68.71 ± 1.28%), inhibition of lipoxygenase activity (75.96 ± 7.64 mg/mL) and interfered the interaction of SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (48.04 ± 3.18%). Furthermore, in-silico analysis results supported that liquiritin, 3,5-dicaffeoylquinic acid, and luteolin-7-O-glucoside with the highest affinity between SARS-CoV-2 RBD and human angiotensin-converting enzyme II (hACE2) receptor. Our findings suggest that PAFYY has the potential for anti-SARS-CoV-2 infection, anti-oxidation stress, and anti-inflammation, and may be used as supplements for amelioration or prevention of COVID-19 symptoms, as well as the representative compounds can be used for quality control of PAFYY in the future. [ABSTRACT FROM AUTHOR]

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5 % and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1–9). Then, both the CC50 and IC50 values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4'-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC50 value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC50 values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (Mpr°) receptors of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12–18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 μg. A booster was given at 5 months after the second dose using either 10 or 15 μg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID50) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9–16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761–3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67–0.97) in 3wPZ30/20; 1.00 (95% CI 0.83–1.20) in 3wPZ20/20; 1.37 (95% CI 1.13–1.65) in 6wPZ30/30; 1.24 (95% CI 1.02–1.50) in 6wPZ30/20; and 1.36 (1.13–1.64) in 6wPZ20/20. After a booster dose with 15 μg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4–94.9) and 331 (95% CI 221–495), respectively. In the group that received 10 μg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0–91.6) and pVNT was 397 (95% CI 267–590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option. [ABSTRACT FROM AUTHOR]

(±)-Decumicorine A (1) and (±)-epi-decumicorine A (2), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purified from the rhizomes of Corydalis decumbens. The separation of (±)-1 and (±)-2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute configurations of compounds (−)-1, (+)-1, (−)-2, and (+)-2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verified by a biomimetic synthesis. Moreover, compound (+)-1 exhibited an antiviral entry effect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2h host cells. [ABSTRACT FROM AUTHOR]

Background: The rapid evolution of SARS-CoV-2 imposed a huge challenge on disease control. Immune evasion caused by genetic variations of the SARS-CoV-2 spike protein's immunogenic epitopes affects the efficiency of monoclonal antibody-based therapy of COVID-19. Therefore, a rapid method is needed to evaluate the efficacy of the available monoclonal antibodies against the new emerging variants or potential novel variants., Objective: The aim of this study is to develop a rapid computational method to evaluate the neutralization power of anti-SARS-CoV-2 monoclonal antibodies against new SARS-CoV-2 variants and other potential new mutations., Methods: The amino acid sequence of the extracellular domain of the spike proteins of the severe acute respiratory syndrome coronavirus (GenBank accession number YP&#95;009825051.1) and SARS-CoV-2 (GenBank accession number YP&#95;009724390.1) were used to create computational 3D models for the native spike proteins. Specific mutations were introduced to the curated sequence to generate the different variant spike models. The neutralization potential of sotrovimab (S309) against these variants was evaluated based on its molecular interactions and Gibbs free energy in comparison to a reference model after molecular replacement of the reference receptor-binding domain with the variant's receptor-binding domain., Results: Our results show a loss in the binding affinity of the neutralizing antibody S309 with both SARS-CoV and SARS-CoV-2. The binding affinity of S309 was greater to the Alpha, Beta, Gamma, and Kappa variants than to the original Wuhan strain of SARS-CoV-2. However, S309 showed a substantially decreased binding affinity to the Delta and Omicron variants. Based on the mutational profile of Omicron subvariants, our data describe the effect of the G339H and G339D mutations and their role in escaping antibody neutralization, which is in line with published clinical reports., Conclusions: This method is rapid, applicable, and of interest to adapt the use of therapeutic antibodies to the treatment of emerging variants. It could be applied to antibody-based treatment of other viral infections., (©Dana Ashoor, Maryam Marzouq, M-Dahmani Fathallah. Originally published in JMIR Bioinformatics and Biotechnology (https://bioinform.jmir.org), 10.10.2024.)

SARS-CoV-2 is a highly contagious and pathogenic virus that first appeared in late December 2019 and caused a global pandemic in a short period. The virus is a single-stranded RNA virus belonging to the Coronaviridae family. Numerous treatments have been developed and tested in response to the pandemic, particularly antiviral drugs. Among them, GS441524 (GS441), a nucleoside antiviral drug, has demonstrated promising results in inhibiting SARS-CoV-2. Nevertheless, the limited oral bioavailability of GS441 restricts its application to patients with the virus. In this study, a novel prodrug of GS441 (NGP-1) with an isobutyl ester and cyclic carbonate structure was designed and synthesized. Its purity and the stability in different artificial digestive juices of NGP-1 was determined with HPLC-DAD methods. The pharmacokinetics of NGP-1 and GS441 were studied in rats via gavage administration. A new LC-MS/MS method was developed to quantitatively analyze GS441 in plasma samples. The results showed that the ka, Cmax, and MRT of converted GS441 from NGP-1 were 5.9, 3, and 2.5 times greater than those of GS441 alone. The Frel of NGP-1 was approximately four-fold that of GS441, with an AUC0–∞ of 9716.3 h·ng mL−1. As a prodrug of GS441, NGP-1 increased its lipophilicity, absorption, and bioavailability, indicating that it holds promise in improving the clinical efficacy of anti-SARS-CoV-2 medications.

Abstract Background Seroprevalence of anti-SARS-CoV-2 antibodies is now available in several world regions to better estimate transmission dynamics. However, to date, there is no epidemiological data regarding anti-SARS-CoV-2 prevalence in Mexico. Therefore, we aimed to determine the prevalence of anti-SARS-CoV-2 antibodies and define the clinical and demographic characteristics associated with seroprevalence. Methods We conducted a cross-sectional serological survey in Ciudad Guadalupe, NL, Mexico. City government employees voluntarily participated during July 2020. Demographic and clinical characteristics were collected at the time of blood sampling to analyze the associated characteristics. IgM/IgG antibodies were determined using a qualitative chemiluminescent immunoassay. Descriptive statistics were used for categorical and continuous variables. Statistical significance was tested using the Chi-squared test, Student’s t-test and the Mann–Whitney. Logistic regression models and the odds ratios (adjusted and unadjusted) were used to estimate the association of demographic and clinical characteristics. Results Of the 3,268 participants included, 193 (5.9%, 95% CI 5.1–6.8) tested positive for IgM/IgG against SARS-CoV-2. Sex, city of residence, and comorbidities did not show any association with having IgM/IgG antibodies. A total of 114 out of 193 (59.1%) subjects with a positive test were asymptomatic, and the odds of being positive were higher in those who reported symptoms of COVID-19 in the previous four weeks to the survey (OR 4.1, 95% CI 2.9–5.5). Conclusions There is a low rate of SARS-CoV-2 infection among government employees that have continuously been working during the pandemic. Six in ten infections were asymptomatic, and seroprevalence is low and still far from herd immunity. Epidemiological surveillance and preventive measures should be mandatory.

Introduction: The necessity of a booster dose is a matter that has not been as yet illuminated, although it is noted that neutralizing antibody titers decrease over time. We aimed therefore to evaluate antibody titers and seroconversion rates after a booster mRNA vaccine and a booster inactivated vaccine. Methods: A total of 322 participants were divided into three main groups, with two subgroups each, based on their vaccinations and previous infection history. The levels of anti-SARS-CoV-2 Ig-G were analyzed with the Elecsys® Anti-SARS-CoV-2 S assay. Results: The antibody titers showed a linear and significant increase from one vaccine group to the other, displaying progressive changes from group 2IV to group 3IV, and then to group 2IV/mRNA. All of the seronegative participants were in the 2IV(-) subgroup; 93.3% of the participants whose antibody titers were above the upper limit were in the 2IV/mRNA group. Doctors were much more inclined to have a booster dose and mRNA vaccines than nurses. The status of being a doctor increases the rate of having a booster dose 7.8 times; likewise, each annual increase in age increases the rate 1.05 times. Conclusion: Anti-SARS-CoV-2 IgG levels decrease over time. The antibody response rate to only two doses of the inactivated vaccine was meager, so a booster dose is necessary to maintain the effectiveness of inactivated vaccines. The third dose of the vaccine, especially that of the mRNA vaccine, which was found to be much more superior to the inactivated vaccine, should be strongly recommended.