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Background: The respiratory system is the most frequently affected system by COVID-19. However, a variety of extra-pulmonary systems can be influenced by COVID-19 with subsequent morbidity and mortality. Aim: This study aim is to report the most frequent extra pulmonary presentations of COVID-19 with comparison to patients with primary pulmonary presentation. Risk factors for ICU admission in both groups were examined. Methods: In this prospective comparative cross-sectional study, detailed demographics, medical history, clinical assessment, and computed tomography (CT) scan of the chest were done to all recruited patients with COVID-19. Result: This study included a total of 1664 confirmed COVID-19 patients. The patients were categorized into two groups. Patients with pulmonary manifestations included 716 patients while 948 patients presented with extrapulmonary manifestations. Patients in the extrapulmonary group were older. The prevalence of certain chronic comorbid conditions was higher in the extra pulmonary group as cardiac, CNS, hepatic, and renal diseases, while chronic respiratory disorders were more prevalent in the pulmonary group (P value: < 0.0001). No significant difference in CT severity score between both groups. CORAD 5 was predominant in the pulmonary group (P value: < 0.0001). Most cases in both groups required hospital admission either inward or in ICU with higher frequency of ICU admission was observed in the pulmonary group. The significant risk factors for ICU admission in both groups were critically ill category of patients, CT severity, low oxygen saturation level, and the presence of comorbid chronic disease (P < 0.0001 with adjusted Odds ratio). CNS, cardiac, renal, and metabolic dysfunctions exert significant risk for ICU admission in the extrapulmonary group. Conclusion: Atypical or non-respiratory manifestations could be the presentation of a respiratory pathogen as reported in COVID-19. Our work highlights the extrapulmonary presentation of COVID-19. Older male patients were more prone to present with extra pulmonary symptoms. CNS, cardiac, renal, and metabolic dysfunctions were the most affected systems. This could impact the level of care required for patient management and the extent of resource utility. [ABSTRACT FROM AUTHOR]

Aim: To study the prevalence and patterns of problematic gaming and gambling during the COVID-19 pandemic and the association with psychiatric traits and major types of anxiety categories. Method: 1067 young adults participated in both wave 3 (2018) and wave 4 (2021) of the SALVe Cohort. Associations with psychiatric symptoms and anxiety were examined using logistic regression and Chi-square tests. Results: Problematic gaming decreased by 1.3 percentage points to 23.2% since the start of the pandemic, while problematic gambling increased by 0.9 percentage points to 6.5% in w4. Average time spent playing video games/day decreased from 2.2 h (w3) to 1.7 h (w4), while increases in gaming activity were associated with worsened feelings of loneliness (p = 0.002), depression (p < 0.001), and anxiety (p < 0.01) during the pandemic. Predictors for problematic gaming at w4 were previous problematic gaming and social anxiety (p = < 0.001 and 0.01, respectively). Moreover, previous problem gambling also predicted problem gambling at w4 p < 0.001. All anxiety categories were associated with both problematic gaming and gambling when adjusted for age and sex. However, after adjusting for depression and insomnia, social anxiety was associated with problematic gaming (p < 0.001), while panic was associated with problem gambling (p < 0.001). Conclusion: Overall, problematic gaming has decreased since the start of the pandemic, while problem gambling has increased. Worsened feelings of loneliness, depression, and anxiety during the pandemic are associated with increased gaming. Moreover, the association between problematic gaming and gambling and anxiety is independent of depression and sleep problems. [ABSTRACT FROM AUTHOR]

Background: Psychological morbidity has been documented in medical and pharmaceutical undergraduate students in different countries around the world. In this study, we examined the impact of coronavirus disease 2019 (COVID-19) home quarantine on the depressive psychological aspects of last-grade pharmacy students. Methods: A cross-sectional study was conducted by the Department of Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Egypt. Two hundred and sixty-eight last-grade pharmacy students were included in this study, and they completed a self-administered, pre-designed, anonymous questionnaire. The main outcome measures were the Hamilton Depression Rating Scale (HRS) and Patient Health Questionnaire-9 (PHQ-9), which were measured to screen for the symptoms of psychological depression and determine the degree of depression severity between the beginning and the end of the COVID-19 home quarantine period. Data entry and analysis were done using the Statistical Package for Social Science (SPSS) software version 26. Descriptive statistics were employed for analyses of the data, and categorical variables were described by frequencies and percentages. Bivariate and multivariable analyses were performed to examine relations between demographic data and psychological scales. The study protocol was approved by the Faculty of Pharmacy, Minia University Ethical Committee. Results: A total of 268 students participated in this study (102 males and 166 females). The mean ± SD score of baseline HRS and HRS at the end of the study was 6.3 ± 4.45, 7.95 ± 5.36, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The mean ± SD score of baseline PHQ-9 and PHQ-9 at the end of the study was 4.35 ± 3.45, 5.37 ± 4.14, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The results showed that the COVID-19 home quarantine period led to a depressive psychological effect on the students in this study. Conclusions: Students' psychological depression causes morbidity and, in some cases, mortality. Psychological depressive problems were significantly associated with the COVID-19 home quarantine period, which calls for early intervention to solve it. Student counselling services must be more accessible and affordable to overcome this problem. [ABSTRACT FROM AUTHOR]

Background: Psychological morbidity has been documented in medical and pharmaceutical undergraduate students in different countries around the world. In this study, we examined the impact of coronavirus disease 2019 (COVID-19) home quarantine on the depressive psychological aspects of last-grade pharmacy students. Methods: A cross-sectional study was conducted by the Department of Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Egypt. Two hundred and sixty-eight last-grade pharmacy students were included in this study, and they completed a self-administered, pre-designed, anonymous questionnaire. The main outcome measures were the Hamilton Depression Rating Scale (HRS) and Patient Health Questionnaire-9 (PHQ-9), which were measured to screen for the symptoms of psychological depression and determine the degree of depression severity between the beginning and the end of the COVID-19 home quarantine period. Data entry and analysis were done using the Statistical Package for Social Science (SPSS) software version 26. Descriptive statistics were employed for analyses of the data, and categorical variables were described by frequencies and percentages. Bivariate and multivariable analyses were performed to examine relations between demographic data and psychological scales. The study protocol was approved by the Faculty of Pharmacy, Minia University Ethical Committee. Results: A total of 268 students participated in this study (102 males and 166 females). The mean ± SD score of baseline HRS and HRS at the end of the study was 6.3 ± 4.45, 7.95 ± 5.36, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The mean ± SD score of baseline PHQ-9 and PHQ-9 at the end of the study was 4.35 ± 3.45, 5.37 ± 4.14, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The results showed that the COVID-19 home quarantine period led to a depressive psychological effect on the students in this study. Conclusions: Students' psychological depression causes morbidity and, in some cases, mortality. Psychological depressive problems were significantly associated with the COVID-19 home quarantine period, which calls for early intervention to solve it. Student counselling services must be more accessible and affordable to overcome this problem. [ABSTRACT FROM AUTHOR]

Many of the survivors of the novel coronavirus disease (COVID-19) are suffering from persistent symptoms, causing significant morbidity and decreasing their quality of life, termed "post-COVID-19 syndrome" or "long COVID". Understanding the mechanisms surrounding PCS is vital to developing the diagnosis, biomarkers, and possible treatments. Here, we describe the prevalence and manifestations of PCS, and similarities with previous SARS epidemics. Furthermore, we look at the molecular mechanisms behind the neurological features of PCS, where we highlight important neural mechanisms that may potentially be involved and pharmacologically targeted, such as glutamate reuptake in astrocytes, the role of NMDA receptors and transporters (EAAT2), ROS signaling, astrogliosis triggered by NF-κB signaling, KNDy neurons, and hypothalamic networks involving Kiss1 (a ligand for the G-protein-coupled receptor 54 (GPR54)), among others. We highlight the possible role of reactive gliosis following SARS-CoV-2 CNS injury, as well as the potential role of the hypothalamus network in PCS manifestations. [ABSTRACT FROM AUTHOR]

Recent evidence points to a potential therapeutic role for glycyrrhizin(GR) and boswellic acids (BA) in the treatment of COVID-19 but conclusive evidence is lacking. Our aim is to investigate the efficacy of GR + BA versus placebo for the treatment of hospitalized patients with moderate SARS-CoV-2 or COVID-19 variants infection. The current study is a randomized, double-blind, placebo-controlled, single-center trial. Patients with SARS-CoV-2 or COVID-19 variants diagnosed by PCR test who were admitted to Sohag University hospital were eligible if they were at least 18 years of age and had moderate symptoms. Patients were randomly assigned to receive oral GR capsule (60 mg) and BA (200 mg) twice daily for 14 days or a matching placebo. All patients also received treatment with the institutional protocol for COVID-19. The primary outcome was mortality and time to recovery. Secondary outcome was clinical status score, 14 days after receiving study drugs. Adverse events from use of study drugs have been evaluated for up to 14 days. The trial is registered at ClinicalTrials.gov (Identifier NCT04487964). During the 6-month enrollment period (June-November, 2021) only 50 patients (54% women; median age 60 years, IQR 54–65) met eligibility and were randomly assigned. Evaluation of the primary outcome at 14 days showed that there were five deaths in the placebo group and no deaths in the GR + BA group. With regard to recovery time, it was significantly shorter (p = 0.0001) in the group receiving GR + BA capsule compared to the placebo group (median 7.0; IQR 6.0–8.0 days vs. median 12.5; IQR 12–20 days). Clinical status on the ordinal score scale as a secondary outcome showed a significant difference between the GR + BA group (median (IQR) score, 2 [2–3]) and placebo groups (mean (IQR) score, 3 [3–5.5]). There was a significant decrease in CRB (p = 0.000041) in GR + BA compared with the placebo group. In conclusion, this safe, inexpensive, antiviral, immunomodulating and anti-inflammatory combination may be considered for use in mild to moderate infections of SARS-CoV-2 or COVID-19 variants. The study is limited by the small sample size; therefore, larger randomized trials are required. [ABSTRACT FROM AUTHOR]

The most severe cases of COVID-19, and the highest rates of death, are among the elderly. There is an urgent need to search for an agent to treat the disease and control its progression. Boswelliaserrata is traditionally used to treat chronic inflammatory diseases of the lung. This review aims to highlight currently published research that has shown evidence of potential therapeutic effects of boswellic acids (BA) and B. serrata extract against COVID-19 and associated conditions. We reviewed the published information up to March 2021. Studies were collected through a search of online electronic databases (academic libraries such as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Several recent studies reported that BAs and B. serrata extract are safe agents and have multiple beneficial activities in treating similar symptoms experienced by patients with COVID-19. Because of the low oral bioavailability and improvement of buccal/oral cavity hygiene, traditional use by chewing B. serrata gum may be more beneficial than oral use. It is the cheapest option for a lot of poorer people. The promising effect of B. serrata and BA can be attributed to its antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, anti-platelet aggregation, antibacterial, antifungal, and broad antiviral activity. B. serrata and BA act by multiple mechanisms. The most common mechanism may be through direct interaction with IκB kinases and inhibiting nuclear factor-κB-regulated gene expression. However, the most recent mechanism proposed that BA not only inhibited the formation of classical 5-lipoxygenase products but also produced anti-inflammatory LOX-isoform-selective modulators. In conclusion a small to moderate dose B. serrata extract may be useful in the enhancing adaptive immune response in mild to moderate symptoms of COVID-19. However, large doses of BA may be beneficial in suppressing uncontrolled activation of the innate immune response. More clinical results are required to determine with certainty whether there is sufficient evidence of the benefits against COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CLpro (Mpro). The drug candidate PF-00835231 is the active compound of the first anti-3CLpro regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the preclinical 3CLpro inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A5491ACE2 cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A5491ACE2 cells and validates PF-00835231's early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231's efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A5491ACE2 cells or human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in nonhuman in vitro models. [ABSTRACT FROM AUTHOR]

Background: COVID-19 vaccination is a crucial public health intervention to stem the pandemic, however, there is a public hesitation to take the vaccine all over the world because of concerns about safety. Objective(s): To assess the intention to take COVID-19 vaccines among adults in Saudi Arabia, and to explore determinants of this intention and causes of refusal of COVID-19 vaccines. Methods: A cross-sectional study was conducted among 1345 adults in all provinces of Saudi Arabia using a questionnaire that was distributed via all social media channels. Stepwise binary logistic regression analysis was performed to identify the predictors to accept COVID-19 vaccination. Results: About 48% of respondents intend to receive COVID-19 vaccines. The predictors of COVID-19 vaccines acceptance were perception of strong possibility of getting COVID-19 infection, high risk perception of the COVID-19, adherence to protective measures during the pandemic, receiving flu vaccines and high level of knowledge. The three most common causes of refusal to receive COVID-19 vaccines were fear from side effects of vaccines (76.8%), absence of trust that it will prevent COVID-19 infection (44%) and being in good health (28.7%). Conclusion and recommendations: The willingness of adults to receive COVID-19 vaccines is suboptimal. There is a need for targeted health education messages using a multidisciplinary team capable of good communication with the public and dissemination of accurate messages via all social media platforms to correct misconceptions about the vaccines especially that related to public confidence in vaccine safety. [ABSTRACT FROM AUTHOR]

Several neurological symptoms and complications have been described in association with COVID-19, such as anosmia, ageusia, encephalitis and Guillain-Barré syndrome. Here, we review the literature describing SARS-CoV-2-induced neurological manifestations and provide a comprehensive discussion of proposed mechanisms underlying the neurological pathophysiology. First, we analyse the neuroinvasiveness potential of the coronavirus family based on previous SARS-CoV-1 studies. Then, we describe the current evidence on COVID-19-induced nervous tissue damage, including processes behind brain vasculopathy and cytokine storm. We also discuss in detail anosmia and Guillain-Barré syndrome. Finally, we provide a summarised timeline of the main findings in the field. Future perspectives are presented, and suggestions of further investigations to clarify how SARS-COV-2 can affect the CNS. [ABSTRACT FROM AUTHOR]

The outbreak of the COVID-19 pandemic has affected the safety and well-being of healthcare workers. A scoping review was conducted to highlight the impact of COVID-19 on the safety, health, and well-being of healthcare workers and to shed light on the concerns about their perceived safety and support systems. A literature search was conducted in three different databases from December 1, 2019, through July 20, 2022, to find publications that meet the aim of this review. Using search engines, 3087 articles were identified, and after a rigorous assessment by two reviewers, 30 articles were chosen for further analysis. Two themes emerged during the analysis: safety and health and well-being. The primary safety concern of the staff was mostly about contracting COVID- 19, infecting family members, and caring for patients with COVID-19. During the pandemic, the health care workers appeared to have anxiety, stress, uncertainty, burnout, and a lack of sleep. Additionally, the review focused on the suggestions of health care providers to improve the safety and well-being of workers through fair organizational policies and practices and timely, individualized mental health care. [ABSTRACT FROM AUTHOR]

Background and objective: People with rheumatic diseases are particularly concerned with the coronavirus disease 2019 (COVID‐19) pandemic. Our work aimed to study the impact of pre‐existing autoimmune rheumatic disease (AIRD) and its immunosuppressive drugs on COVID‐19 severity and outcome. Patients and methods: This is a multicenter case‐control study performed between September 2020 and February 2021 on 130 adults with COVID‐19, including 66 patients with AIRD and 64 without AIRD, who served as a control group. Results: Regarding COVID‐19 clinical manifestations; diarrhea, fatigue, and headache were found with significantly higher frequency in the AIRD group while a higher frequency of cough was found in the control group. Comparing COVID‐19 complications, only septic shock was significantly higher in the AIRD group (P = 0.013). Both groups were treated with similar COVID‐19 drugs except for tocilizumab and anticoagulants, which were statistically significantly more frequently used in the control group (P < 0.001 for both). No statistically significant difference was found between the groups in the outcome or severity of COVID‐19. There was no impact of previous immunosuppressive drugs before COVID‐19 on the severity of the disease except for a longer duration of recovery in patients on steroids (P < 0.001). Patients with hypertension had severe COVID‐19 compared with those without (odds ratio 2.8, 95% confidence interval 1.2‐6.9; P = 0.020). Conclusion: AIRD may not affect COVID‐19 severity and outcome. Similarly, immunosuppressive medications had no effect; except that patients on systemic steroids had longer duration for recovery. Comorbid conditions, such as hypertension, may be associated with more severe COVID‐19 disease course. [ABSTRACT FROM AUTHOR]

Alkyl phenylcarbamodithioates were reacted with hydrazonoyl bromide 1a, b in ethanol containing a catalytic amount of triethylamine solution to afford and 1,3,4-thiadiazole derevatives 5a, b, respectively. In the same manner, alkyl hydrazinecarbodithioate (6–10)a, b were reacted with the appropriate hydrazonoyl bromide (1a, b) in ethanol containing a catalytic amount of triethylamine solution to afford 1,3,4-thiadiazole derivatives (13–17), respectively. Moreover, hydrazonoyl bromide 1a or 1b was reacted with 5-phenyl-1,3,4-oxadiazole-2-thione 22A in refluxing chloroform containing triethylamine to give 1,3,4-thiadiazole derivatives 21a and b, respectively. Elemental analysis, spectral data, and an alternative synthetic route were used to confirm the structures of all the newly synthesized heterocyclic compounds. AutoDock was used to screen possible drugs. To screen potential medications, AutoDock was utilized. The antiviral medications chloroquine, hydroxychloroquine, and Lopinavir, as well as their synthesized components, were all tested. Confirmation comes from molecular docking and computational investigations. The results of a detailed exploration of the structural characterization of 5b and 13b using quantum chemistry methods calculated using the DFT (B3LYP) method with a 6-31 + g (d, p) basis set are presented in the computational study. The goal of this study was to investigate the molecular dynamics and structural characteristics that regulate chemical behavior, as well as to compare theoretical predictions with experimental results. [ABSTRACT FROM AUTHOR]

Recently, the SARS-CoV-2 (COVID-19) pandemic virus has been spreading throughout the world. Until now, no certified drugs have been discovered to efficiently inhibit the virus. The scientists are struggling to find new safe bioactive inhibitors of this deadly virus. In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3-chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting enzyme 2 (ACE2) receptor (1R42), which is the entry point for the viral encounter, were studied with the prospects of identifying significant drug candidate(s) against COVID-19 infection. Then, the protein stability produced score of less than 0.6 for all residues of all studied receptors. This confirmed that these receptors are extremely stable proteins, so it is very difficult to unstable the stability of these proteins through utilizing individual drugs. Hence, we studied the combination and tricombination therapy between bioactive compounds which have the best binding affinity and some antiviral drugs like chloroquine, hydroxychloroquine, azithromycin, simeprevir, baloxavir, lopinavir, and favipiravir to show the effect of combination and tricombination therapy to disrupt the stability of the three major viral targets that are mentioned previously. Also, ADMET study suggested that most of all studied bioactive compounds are safe and nontoxic compounds. All results confirmed that caulerpin can be utilized as a combination and tricombination therapy along with the studied antiviral drugs for disrupting the stability of the three major viral receptors (6LU7, 6VYB, and 1R42). [ABSTRACT FROM AUTHOR]

Most of the post‐renal transplant patients are taking immunosuppressive medications, including calcineurin inhibitors, anti‐proliferative agents, and steroids. This case series highlights the clinical characteristics and outcomes of eight post‐renal transplant patients with severe COVID‐19 infection admitted to the intensive care unit. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1–6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate. [ABSTRACT FROM AUTHOR]

This case highlights an atypical presentation of a patient with unknown history of mental disease who has been diagnosed with a bipolar disorder associated with severe COVID‐19 symptoms. Neuroimaging was only positive for subtle white matter changes; he was treated with antipsychotics and mood‐stabilizing agents until he reached partial remission. The authors urge clinicians to consider the impact of the COVID‐19 pandemic on patients with mental illness and the urgent need for vigilant monitoring of presenting signs and symptoms. [ABSTRACT FROM AUTHOR]

Pregnant women are potentially more susceptible to respiratory tract infections making them a high‐risk group. We describe the successful management of a 35‐year‐old pregnant woman, G3, P1, with a history of a cesarean section who tested positive for COVID‐19 at 26 weeks and required critical care support. [ABSTRACT FROM AUTHOR]

The authors urge clinicians to observe for early signs of CMV reactivation in patients presenting with gastrointestinal bleeding and intestinal perforation after receiving tocilizumab or other immunosuppressive therapy as a treatment for COVID 19. Early recognition of CMV infection and treatment will prevent life‐threatening bleeding and mortality. [ABSTRACT FROM AUTHOR]

Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of these drugs by using caulerpin and its derivatives as an adjunct drug against SARS-CoV-2 receptor proteins: the SARS-CoV-2 main protease and the SARS-CoV-2 spike protein. Caulerpin exhibited antiviral activities against chikungunya virus and herpes simplex virus type 1. Caulerpin and some of its derivatives showed inhibitory activity against Alzheimer's disease. The web server ANCHOR revealed higher protein stability for the two receptors with disordered score (< 0.6). Molecular docking analysis showed that the binding energies of most of the caulerpin derivatives were higher than all the suggested drugs for the two receptors. Also, we deduced that inserting NH2, halogen, and vinyl groups can increase the binding affinity of caulerpin toward 6VYB and 6LU7, while inserting an alkyl group decreases the binding affinity of caulerpin toward 6VYB and 6LU7. So, we can modify the inhibitory effect of caulerpin against 6VYB and 6LU7 by inserting NH2, halogen, and vinyl groups. Based on the protein disordered results, the SARS-CoV-2 main protease and SARS-CoV-2 spike protein domain are highly stable proteins, so it is quite difficult to unstabilize their integrity by using individual drugs. Also, molecular dynamics (MD) simulation indicates that binding of the combination therapy of simeprevir and the candidate studied compounds to the receptors was stable and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. So, this study suggested that caulerpin and its derivatives could be used as a combination therapy along with lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir for disrupting the stability of SARS-CoV2 receptor proteins to increase the antiviral activity of these drugs. [ABSTRACT FROM AUTHOR]

This work aimed at evaluating the inhibitory effect of ten natural bioactive compounds (1–10) as potential inhibitors of SARS-CoV-2-3CL main protease (PDB ID: 6LU7) and SARS-CoV main proteases (PDB IDs: 2GTB and 3TNT) by molecular docking analysis. The inhibitory effect of all studied compounds was studied with compared to some proposed antiviral drugs which currently used in COVID-19 treatment such as chloroquine, hydroxychloroquine, azithromycin, remdesivir, baloxvir, lopinavir, and favipiravir. Homology modeling and sequence alignment was computed to evaluate the similarity between the SARS-CoV-2-3CL main protease and other SARS-CoV receptors. ADMET properties of all studied compounds were computed and reported. Also, molecular dynamic (MD) simulation was performed on the compound which has the highest binding affinity inside 6LU7 obtained from molecular docking analysis to study it is stability inside receptor in explicit water solvent. Based on molecular docking analysis, we found that caulerpin has the highest binding affinity inside all studied receptors compared to other bioactive compounds and studied drugs. Our homology modeling and sequence alignment showed that SARS-CoV main protease (PDB ID: 3TNT) shares high similarity with 3CLpro (96.00%). Also, ADMET properties confirmed that caulerpin obeys Lipinski's rule and passes ADMET property, which make it a promising compound to act as a new safe natural drug against SARS-CoV-2-3CL main protease. Finally, MD simulation confirmed that the complex formed between caulerpin and 3CLpro is stable in water explicit and had no major effect on the flexibility of the protein throughout the simulations and provided a suitable basis for our study. Also, binding free energy between caulerpin and 6LU7 confirmed the efficacy of the caulerpin molecule against SARS-CoV-2 main protease. So, this study suggested that caulerpin could be used as a potential candidate in COVID-19 treatment. [ABSTRACT FROM AUTHOR]

The authors urge clinicians to balance the use of Immunosuppressant drugs and tocilizumab for COVID‐19 patients to avoid the development of infections like Cryptococcemia, leading to death within 30 days. [ABSTRACT FROM AUTHOR]