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This study investigates organotin (IV) complexes derived from the recently synthesized quinazoline Schiff base ligand (L). The research involves synthesizing and characterizing these complexes, including elemental analysis, UV–visible, FT‐IR, mass spectra, and conductometric measurements. Advanced studies such as density functional theory (DFT) are employed to gain insights into the stable electronic configuration. Specifically, the study explores the proposed geometry, revealing a distorted octahedral structure for the complexes. The findings contribute as critical molecular characteristics of these newly synthesized complexes, paving the way for potential applications in diverse fields, including medicinal chemistry. Through an investigation into the antimicrobial properties, the efficacy of the synthesized compounds was assessed against a diverse range of bacterial and fungal strains. Remarkably, the complexes demonstrated significant antimicrobial activities, showing potential applications in combating various microbial infections. In an extended exploration of their medical utility, the compounds were examined for their antibiotic properties against Helicobacter pylori. The Schiff base and its metal complexes emerged as promising antibiotics with notable efficacy against H. pylori, suggesting their potential in addressing infections associated with this bacterium. Furthermore, the antitumor potential of the synthesized complexes was investigated, focusing on their impact on MCF‐7 (Breast carcinoma) cells. The organotin (IV) Schiff base complexes in this research showed remarkable efficacy, evidenced by their notably low IC50 values (9, 10, 11 μg/mL) in comparison with cisplatin. In addition to their potent antitumor effects, these complexes exhibited reduced cytotoxicity toward normal cells (VERO cells) compared with cisplatin. The investigation extends to molecular docking, where this approach aims to elucidate their interactions with specific protein structures, including (2JFZ, 1SC7, and 6W41). The primary objective is to clarify the potential properties of these compounds, focusing on their antibiotic efficacy, anti‐H. pylori activity, antitumor potential, and anti‐COVID‐19 properties. [ABSTRACT FROM AUTHOR]

Mixed ligand complexes of manganese(II), cobalt(II), copper(II), and cadmium(II)with an innovative Schiff base ligand denoted as (L1), 4-(2-((1E,2E)-1-(2-(p-tolyl)hydrazineylidene)propan-2-ylidene)hydrazineyl), served as the principal ligand, while glycine (L2) was employed as secondary ligand were successfully effectively characterized through a comprehensive set of analyses, including Elemental analysis, UV–Visible, FT-IR, Mass spectra, and conductometric measurements. Density functional theory (DFT) computations were executed to discern the enduring electronic arrangement, the energy gap, dipole moment and chemical hardness of the hybrid ligand assemblies. The proposed geometry for the complexes is a distorted octahedral structure. The antimicrobial efficacy of these compounds was assessed against a range of bacterial and fungal strains. Notably, these complexes exhibited promising antimicrobial activities, with the cadmium (II) complex demonstrating superior efficacy towards all tested organisms. These compounds were also examined for their antibiotic properties against H. pylori to explore their broader medical potential. The Schiff base ligand and its corresponding metal complexes displayed substantial potential as an antibiotic against H. pylori. Additionally, the antitumor potential of the synthesized complexes was assessed against MCF-7 (Breast carcinoma) cells—the Cu (II) complex demonstrated superior activity with the lowest IC50 value compared to cisplatin. Moreover, it exhibited reduced cytotoxicity towards normal cells (VERO cells) compared to cisplatin, establishing it as the most potent compound in the study. Furthermore, molecular docking was explored of the Schiff base ligand and its corresponding cadmium(II) complex. The analysis of the docking study yielded valuable structural insights that can be effectively utilized in conducting inhibition studies for example against COVID-19. This comprehensive study highlights these synthesized compounds' multifaceted applications and promising bioactive properties. [ABSTRACT FROM AUTHOR]

Novel benzidine bis azo (BBA) complexes with Fe(III), Co(III), Ni(II), Cu(II), and Zn(II) were created and analyzed using a variety of analytical methods. The B3LYP/6-311G(d,p) and LANL2DZ basis sets were used in quantum chemical simulations with the DFT approach to analyze the structures of the BBA and its complexes. The compounds' strong NLO properties can be easily polarized, as indicated by the narrow HOMO-LUMO energy gap. The polarizability and hyperpolarizabilities of the chelates indicate that they are good candidates for NLO materials. The electronic spectra were computed using the polarizable continuous solvation method PCM, TD-DFT/PCM. Additionally, the infrared spectra obtained were compared to the anticipated harmonic vibrations of the azo dye ligand and its complexes. Utilizing molecular docking and virtual screening technologies, binding energy studies of the bis azo dye ligand and its complexes with the human coronavirus Nl63 nucleocapsid protein (PDB ID: 5epw) and SARS-CoV spike protein (PDB ID: 5wrg) were anticipated. The results demonstrated promising binding. The outcomes demonstrated the efficiency of the ligand and its complexes as COVID-19 and SARS virus inhibitors. Zn was shown to be the only metal that connected to the 5epw-Viral protein. [ABSTRACT FROM AUTHOR]

Corona Virus Disease 19 (COVID-19) has been a major pandemic impacting a huge population worldwide, and it continues to present serious health threats, necessitating the development of novel protective nutraceuticals. Biobran/MGN-3, an arabinoxylan rice bran, is a potent immunomodulator for both humans and animals that has recently been demonstrated to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We here investigate Biobran/MGN-3′s potential to enhance an antiviral immune response in humans. Peripheral blood mononuclear cells (PBMCs) derived from eight subjects taking Biobran/MGN-3 (age 55–65 years) and eight age-matched control subjects were stimulated with irradiated SARS-CoV-2 virus and then subjected to immuno-phenotyping and multiplex cytokine/chemokine assays. Results showed that PBMCs from subjects supplemented with Biobran/MGN-3 had significantly increased activation of plasmacytoid dendritic cells (pDCs) coupled with increased IFN-α secretion. We also observed higher baseline expression of HLA-DR (human leukocyte antigen-DR isotype) on dendritic cells (DCs) and increased secretion of chemokines and cytokines, as well as a substantial increase in cytotoxic T cell generation for subjects taking Biobran/MGN-3. Our results suggest that Biobran/MGN-3 primes immunity and therefore may be used for boosting immune responses against SARS-CoV-2 infections and other diseases, particularly in high-risk populations such as the elderly. [ABSTRACT FROM AUTHOR]

Due to inadequate pharmaceutical wastewater treatment, anticancer contaminants from the pharmaceutical industry frequently end up in the aquatic environment where they endanger aquatic life and humans. As a result, the appropriate treatment of wastewater that contains anticancer agents is crucial for pollution prevention. The purpose of this work is to assess the effectiveness of a Fe3O4@ZIF-8 nanocomposite as an adsorbent to remove of the chemotherapeutic drugs doxorubicin (DOX) from aqueous solution. SEM, XRD, BET, FT-IR, Zeta potential, and point of zero charge analysis were used to study the surface and structural characteristics of the Fe3O4@ZIF-8 nanocomposite. Via the proposed treatment, 804.84 mg/g elimination was successful under the following circumstances: pH = 6; Fe3O4@ZIF-8 dose = 0.02 g/25 mL; DOX concentration = 1.22x10−3 mol; adsorption time = 100 min; and shaking speed = 200 rpm. A investigation of isotherms shown that the Langmuir equation and experimental data suited each other quite well. The adsorption of DOX on Fe3O4@ZIF-8 was endothermic and spontaneous, in accordance with thermodynamic properties. Furthermore, the elimination of DOX was enhanced by the rise in solution temperature. The kinetic analysis revealed that the pseudo-second order was fitted by the model. The suggested adsorption method could recycle Fe3O4@ZIF-8 nanocomposite six times, with a modest reduction in its ability for adsorption. For all XRD reflection peaks, physical characteristics including strain rates were computed and the dislocation of was 4.7 × 10−6. Investigate the activity of the DOX towards COVID-19, breast and prostate cancer using molecular docking. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a new coronavirus in the Coronaviridae family. The COVID-19 pandemic, caused by SARS-CoV-2, has undoubtedly been the largest crisis of the twenty-first century, resulting in over 6.8 million deaths and 686 million confirmed cases, creating a global public health issue. Hundreds of notable articles have been published since the onset of this pandemic to justify the cause of viral spread, viable preventive measures, and future therapeutic approaches. As a result, this review was developed to provide a summary of the current anti-COVID-19 drugs, as well as their timeline, molecular mode of action, and efficacy. It also sheds light on potential future treatment options. Several medications, notably hydroxychloroquine and lopinavir/ritonavir, were initially claimed to be effective in the treatment of SARS-CoV-2 but eventually demonstrated inadequate activity, and the Food and Drug Administration (FDA) withdrew hydroxychloroquine. Clinical trials and investigations, on the other hand, have demonstrated the efficacy of remdesivir, convalescent plasma, and monoclonal antibodies, 6-Thioguanine, hepatitis C protease inhibitors, and molnupiravir. Other therapeutics, including inhaled medicines, flavonoids, and aptamers, could pave the way for the creation of novel anti-COVID-19 therapies. As future pandemics are unavoidable, this article urges immediate action and extensive research efforts to develop potent specialized anti-COVID-19 medications. [ABSTRACT FROM AUTHOR]

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as "long COVID" and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin's anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin's anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25–50 μM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25–50 μM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin's binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development. [ABSTRACT FROM AUTHOR]

Abstract As a multifunctional fluorescent nanomaterial, carbon dots (CDs) not only have small size, stable chemical properties, excellent photoluminescence characteristics, but also exhibit good biocompatibility and low toxicity. It has attracted considerable attention in the field of nanotechnology and biological science. CDs contain abundant functional groups on the surface, which not only retain part of the properties of raw materials, but also may have new photoelectric, catalytic, biomedical, and other functions. In this review, we systematically summarize the synthesis methods, modifications, optical properties, and main biological functions of CDs in recent years. The application of functionalized modified CDs in biological detection, biological imaging, photodynamic therapy, photothermal therapy, targeted therapy, drug delivery, gene delivery, protein delivery, and other biomedical fields is introduced. The latest progress of CDs with its own biomedical function in antioxidant, anti‐pathogen, and disease treatment is summarized. Finally, we discuss some problems in the practical application of CDs and look forward to the future development trend of self‐functional CDs combined with surface modification to achieve multimodal treatment of diseases.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations. SARS-CoV-2 spike is largely hidden in cell organelles, resulting in compromised host immune surveillance. We invented a COPI inhibitor capable of promoting spike surface exposure to enhance host immune response. [Display omitted] [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]

Using anti-COVID-19 mouthwashes has become necessary to reduce acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions. Resin-matrix ceramic (RMCs) materials that are exposed to mouthwashes may affect the bonding of repaired materials. This research was performed to assess the effects of anti-COVID-19 mouthwashes on the shear bond strengths (SBS) of RMCs repaired with resin composites. A total of 189 rectangular specimens of two different RMCs (Vita Enamic (VE) and Shofu Block HC (ShB)) were thermocycled and randomly divided into nine subgroups according to different mouthwashes (distilled water (DW), 0.2% povidone–iodine (PVP-I), and 1.5% hydrogen peroxide (HP)) and surface treatment protocols (no surface treatment, hydrofluoric acid etching (HF), and sandblasting (SB)). A repair protocol for RMCs was performed (using universal adhesives and resin composites), and the specimens were assessed using an SBS test. The failure mode was examined using a stereomicroscope. The SBS data were evaluated using a three-way ANOVA and a Tukey post hoc test. The SBS were significantly affected by the RMCs, mouthwashes, and surface treatment protocols. Both surface treatment protocols (HF and SB) for both RMCs, whether immersed in anti-COVID-19 mouthwash or not, improved the SBS. For the VE immersed in HP and PVP-I, the HF surface treatment had the highest SBS. For the ShB immersed in HP and PVP-I, the SB surface treatment had the highest SBS. [ABSTRACT FROM AUTHOR]

Simple, accurate and robust analytical methods have been developed and validated for the determination of favipiravir (FVPR) by RP-HPLC and UV spectroscopy techniques as per the ICH guidelines. In the RP-HPLC method for FVPR determination, the mobile phase was ammonium acetate buffer pH 6.5 in pump Aand methanol in pump B. The C18 (Sunfire) 5 μm, 4.6 × 250 mm column was used as a stationary phase, and the detection wavelength was at 323 nm. Under these conditions, FVPR was eluted as a sharp peak at 2.65 min and the overall time taken for each injection was 10 min. In case of the UV spectroscopy method, standard FVPR solutions were prepared with pure ethanol and scanned from 250 to 400 nm and a flourishing spectrum was obtained at 323 nm. Hence, the wavelength of 323 nm was fixed for the whole process of validation in both techniques. The limit of detection (LOD) and limit of quantification (LOQ) in the RP-HPLC method were 1.0 and 3.5 μg/mL, respectively, and the linearity was established in the 10 to 50 μg/mL range. In the UV spectroscopy method, the LOD and LOQ values were found to be 3.5 and 12 μg/mL, respectively, and the linearity was established within 20 to 60 μg/mL range. The regression coefficient was found to exceed 0.999 in both methods. The proposed RP-HPLC and UV spectroscopy techniques are simple, accurate, rugged and robust. [ABSTRACT FROM AUTHOR]

IntroductionDue to its high transmissibility and immune escape, Omicron subvariant BA.5 has become the dominant strain of the SARS-CoV-2 virus and led to escalating COVID-19 cases, how to cope with it becomes an urgent issue. A BA.5 infection surge burst out on 18 June 2022 and brought an unprecedented challenge to Macau, the most densely populated region worldwide. This study aimed to analyze the characteristics of this outbreak and summarize the useful anti-epidemic measures and experiences during this outbreak.MethodsAll data were obtained from the Government Portal of Macao SAR (https://www.gov.mo), and the Special Webpage Against Epidemics, the Macao Health Bureau (www.ssm.gov.mo). An epidemiologic study was performed to analyze epidemic outcomes, including the infection rate, the proportion of symptomatic cases, the case fatality ratio (CFR), etc. Data were analyzed using SPSS Version 20. A p-value

The recent emergence of the severe acute respiratory disease caused by a novel coronavirus remains a concern posing many challenges to public health and the global economy. The resolved crystal structure of the main protease of SARS-CoV-2 or SCV2 (Mpro) has led to its identification as an attractive target for designing potent antiviral drugs. Herein, we provide a comparative molecular impact of hydroxychloroquine (HCQ), remdesivir, and β-D-N4-Hydroxycytidine (NHC) binding on SCV2 Mpro using various computational approaches like molecular docking and molecular dynamics (MD) simulation. Data analyses showed that HCQ, remdesivir, and NHC binding to SARS-CoV-2 Mpro decrease the protease loop capacity to fluctuate. These binding influences the drugs' optimum orientation in the conformational space of SCV2 Mpro and produce noticeable steric effects on the interactive residues. An increased hydrogen bond formation was observed in SCV2 Mpro–NHC complex with a decreased receptor residence time during NHC binding. The binding mode of remdesivir to SCV2 Mpro differs from other drugs having van der Waals interaction as the force stabilizing protein–remdesivir complex. Electrostatic interaction dominates in the SCV2 Mpro−HCQ and SCV2 Mpro–NHC. Residue Glu166 was highly involved in the stability of remdesivir and NHC binding at the SCV2 Mpro active site, while Asp187 provides stability for HCQ binding. [ABSTRACT FROM AUTHOR]

Salvia grossheimii is a perennial herb with antidiabetic and cytotoxic constituents. In continuation of our study on S. grosshiemii to identify the bioactive phytochemicals, we have reported the characterization of seven undescribed triterpenoids. The aerial parts of the plant were extracted in dichloromethane and its constituents were isolated using chromatography techniques. The structures of compounds were identified using 1D, 2D NMR, and ESI-MS spectral data. Seven new oleanane- and ursane-type triterpenoids (1–7) were identified in S. grossheimii. The structures of 1–7 were characterized as; 2α-hydroxy-3β-acetoxy-olean-9(11),12-diene (1), 2α-acetoxy-3β-hydroxy-olean-9(11),12-diene (2), 3β-acetoxy-olean-18-ene,2α,11α-diol (3), 2α-hydroxy-3β-acetoxy-urs-9(11),12-diene (4), 2α-acetoxy-3β-hydroxy-urs-9(11),12-diene (5), 2α,3β-diacetoxy-urs-12-ene-11α,20β-diol (6), 2α,3β-diacetoxy-urs-9(11),12-diene-20β-ol (7). Triterpenoids (2, 5, and 7) were intramolecular transesterification or dehydration products of their corresponding isomers or allylic alcohol in the C rings, respectively, produced in-situ during NMR spectroscopy. Virtual screening of 1–7 was performed with molecular docking analysis to identify the potential SARS-CoV-2 and α-glucosidase inhibitors using the smina molecular docking algorithm. The best binding energy values (kcal/mol) against COVID-19 main protease Mpro were calculated for 6 (-8.77) and 7 (-8.68), and the higher binding affinities toward human α-glucosidase were obtained for 2 (-9.39) and 6 (-8.63). This study suggests S. grossheimii as a rich source of bioactive triterpenoids and introduces new natural compounds. Considering the high binding energy values of 2, 6, and 7, these structures could be candidates for anti-COVID-19 and antidiabetic drug development in the future. [ABSTRACT FROM AUTHOR]

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 and became a pandemic in a critically short time. Phenolic secondary metabolites attracted much attention from the pharmaceutical industries for their easily accessible natural sources and proven antiviral activity. In our mission, a metabolomics study of the Garcinia cambogia Roxb. fruit rind was performed using LC-HRESIMS to investigate its chemical profile, especially the polar aspects, followed by a detailed phytochemical analysis, which led to the isolation of eight known compounds. Using spectrometric techniques, the isolated compounds were identified as quercetin, amentoflavone, vitexin, rutin, naringin, catechin, p-coumaric, and gallic acids. The antiviral activities of the isolated compounds were investigated using two assays; the 3CL-Mpro enzyme showed that naringin had a potent effect with IC50 16.62 μg/mL, followed by catechin and gallic acid (IC50 26.2, 30.35 μg/mL, respectively), while the direct antiviral inhibition effect of naringin confirmed the potency with an EC50 of 0.0169 μM. To show the molecular interaction, in situ molecular docking was carried out using a COVID-19 protease enzyme. Both biological effects and docking studies showed the hydrophobic interactions with Gln 189 or Glu 166, per the predicated binding pose of the isolated naringin. [ABSTRACT FROM AUTHOR]

General methods to quantize combined descriptors of both the probability and phase/current distributions in molecular electronic reference frame transformations to a “superposition of coordinate transformations” have been previously introduced. Quantum gravity Continuity equations are expected to resolve the singularities of classical general relativity for these transformations that have been already explored on an array of recent fundamental observations developed through gravitational amplification of primeval density fluctuations generated in the exceedingly early phase of cosmic evolution. Based on destructive interference of singular spacetime-configurations, I show that higher-order vertical-equilibrium states in curvature terms direct me to resolve black-hole singularities for a vanishing current entanglement in a chemical space both in the spherically symmetric and axisymmetric case. Dynamical mechanisms for singularity-resolution and orbital superpositions are considered observer-dependent features in these quantum reference frames including Galilean transformation, and near-horizon symmetries ranging from supergravity theories to Lorentzian cryptographic signatures to enhance the RoccuffirnaTM’s gravity to trap the SARS-COV-2 viruses in practice. The corresponding stationary radial Schrödinger equations with these potential energy functions are solved analytically, in the underlying information continuity equation that determines machine learning characteristics for both Euclidean and Lorentzian signatures to Quantum microBlackHole-Inspired Kerr- (A) dS-Myers–Perry black Gravitational in an approximate scheme for zero total angular momentum. It is also found that the wave functions for bound states can be expressed in terms of the Jacoby polynomial involving either the nonclassical or resultant entropy/information concepts the so called horizontal-equilibrium state, that represents the phase-transformed quantum state of a molecule, corresponding to the optimum, density-dependent “thermodynamic” phase in the near-horizon limit, with either SL(2, ℝ) or Poincaré iso(1, 1) symmetry as extended to the entire near-horizon geometry. In this paper, I propose an implementation of the algorithm for the Quantum Inspired blAckhole ProductS of TaylOr Fast FourIer transforMatIons (QubAPSOFFiMi) as a quantum circuit consisting of a combination of some Lorentzian signature quantum gates. In my implementation, a data sequence is expressed by a tensor product of vector spaces. Namely, my QFFT is defined as a transformation of the tensor product of stationary radial Schrödinger equations with these potential energy functions of quantum states. It is essentially different from the so-called quantum Fourier transform (QFT) defined to be a horizontal-equilibrium state of linear transformation of the amplitudes for the superposition of quantum states. The quantum circuit for the (QubAPSOFFiMi) consists of several circuits for elementary arithmetic operations such as a quantum adder, subtractor and shift operations, which are implemented as effectively as possible. These analytical expressions for purely vibrational energy levels of the electronic state, without an accompanying change of quantum observables, preserves the electron probability distribution and modifies its current by varying the moduli to a weakly-coupled description of a pharmacophoric system, where states with fixed conserved charge charges can be electronically counted. The influence of the continuity chemical relations between equilibrium-phase gravitational transformation, quantum phase density, and local entropy formalism productions are examined here towards Black-Hole Singularity-Mass Schrödinger Equations in a Quantum Kerr- (A) Ds Galilean Myers—Perr driven Lorentzian Gravitational Path for the anti-COVID-19 RoccuffirnaTM and EplerotiffirnaTM molecular equilibrium states in regular black-hole spacetimes. [Figure: see text]

The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, Digoxin, Proscillaridin, Salinomycin and Niclosamide with promising anti-SARS-CoV-2 activity were screened in silico against four SARS-CoV-2 proteins—papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), SARS-CoV-2 main protease (Mpro), and adaptor-associated kinase 1 (AAK1)—in an attempt to define their promising targets. The applied computational techniques suggest that all the tested drugs exhibited excellent binding patterns with higher scores and stable complexes compared to the native protein cocrystallized inhibitors. Ouabain was suggested to act as a dual inhibitor for both PLpro and Mpro enzymes, while Digitoxin bonded perfectly to RdRp. In addition, Salinomycin targeted PLpro. Particularly, Niclosamide was found to target AAK1 with greater affinity compared to the reference drug. Our study provides comprehensive molecular-level insights for identifying or designing novel anti-COVID-19 drugs. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and Omicron spike proteins, in comparison to the reference drugs. In particular, compound 9 has the highest scoring affinity against the SARS-CoV-2 and Omicron spike proteins in vitro with its IC50 reaching 75.98 nM against the Omicron spike protein and 74.51 nM against the SARS-CoV-2 spike protein. The possible interaction between the synthesized triazoles and the viral spike proteins was by the prevention of the viral entry into the host cells, which led to a reduction in viral reproduction and infection. A cytopathic inhibition assay in the human airway epithelial cell line (Vero E6) infected with SARS-CoV-2 revealed the effectiveness and safety of the synthesized compound (compound 9) (EC50 and CC50 reached 80.4 and 1028.28 µg/mL, respectively, with a selectivity index of 12.78). Moreover, the antiinflammatory effect of the tested compound may pave the way to reduce the reported SARS-CoV-2-induced hyperinflammation. [ABSTRACT FROM AUTHOR]

General methods to quantize combined descriptors of both the probability and phase/current distributions in molecular electronic reference frame transformations to a “superposition of coordinate transformations” have been previously introduced. Quantum gravity Continuity equations are expected to resolve the singularities of classical general relativity for these transformations that have been already explored on an array of recent fundamental observations developed through gravitational amplification of primeval density fluctuations generated in the exceedingly early phase of cosmic evolution. Based on destructive interference of singular spacetime-configurations, I show that higher-order verticalequilibrium states in curvature terms direct me to resolve black-hole singularities for a vanishing current entanglement in a chemical space both in the spherically symmetric and axisymmetric case. Dynamical mechanisms for singularity-resolution and orbital superpositions are considered observer-dependent features in these quantum reference frames including Galilean transformation, and near-horizon symmetries ranging from supergravity theories to Lorentzian cryptographic signatures to enhance the RoccuffirnaTM’s gravity to trap the SARS-COV-2 viruses in practice. The corresponding stationary radial Schrödinger equations with these potential energy functions are solved analytically, in the underlying information continuity equation that determines machine learning characteristics for both Euclidean and Lorentzian signatures to Quantum microBlackHole-Inspired Kerr(A) dS-Myers–Perry black Gravitational in an approximate scheme for zero total angular momentum. It is also found that the wave functions for bound states can be expressed in terms of the Jacoby polynomial involving either the nonclassical or resultant entropy/information concepts the so called horizontal-equilibrium state, that represents the phase-transformed quantum state of a molecule, corresponding to the optimum, density-dependent “thermodynamic” phase in the near-horizon limit, with either SL(2, ℝ) or Poincaré iso(1, 1) symmetry as extended to the entire near-horizon geometry. In this paper, I propose an implementation of the algorithm for the Quantum Inspired blAckhole ProductS of TaylOr Fast FourIer transforMatIons (QubAPSOFFiMi) as a quantum circuit consisting of a combination of some Lorentzian signature quantum gates. In my implementation, a data sequence is expressed by a tensor product of vector spaces. Namely, my QFFT is defined as a transformation of the tensor product of stationary radial Schrödinger equations with these potential energy functions of quantum states. It is essentially different from the so-called quantum Fourier transform (QFT) defined to be a horizontalequilibrium state of linear transformation of the amplitudes for the superposition of quantum states. The quantum circuit for the (QubAPSOFFiMi) consists of several circuits for elementary arithmetic operations such as a quantum adder, subtractor and shift operations, which are implemented as effectively as possible. These analytical expressions for purely vibrational energy levels of the electronic state, without an accompanying change of quantum observables, preserves the electron probability distribution and modifies its current by varying the moduli to a weaklycoupled description of a pharmacophoric system, where states with fixed conserved charge charges can be electronically counted. The influence of the continuity chemical relations between equilibrium-phase gravitational transformation, quantum phase density, and local entropy formalism productions are examined here towards Black-Hole Singularity-Mass Schrödinger Equations in a Quantum Kerr(A) Ds Galilean Myers—Perr driven Lorentzian Gravitational Path for the anti-COVID-19 RoccuffirnaTM and EplerotiffirnaTM molecular equilibrium states in regular blackhole spacetimes. [ABSTRACT FROM AUTHOR]

Using anti-COVID-19 mouthwashes has become necessary to reduce acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions. Resin-matrix ceramic (RMCs) materials that are exposed to mouthwashes may affect the bonding of repaired materials. This research was performed to assess the effects of anti-COVID-19 mouthwashes on the shear bond strengths (SBS) of RMCs repaired with resin composites. A total of 189 rectangular specimens of two different RMCs (Vita Enamic (VE) and Shofu Block HC (ShB)) were thermocycled and randomly divided into nine subgroups according to different mouthwashes (distilled water (DW), 0.2% povidone–iodine (PVP-I), and 1.5% hydrogen peroxide (HP)) and surface treatment protocols (no surface treatment, hydrofluoric acid etching (HF), and sandblasting (SB)). A repair protocol for RMCs was performed (using universal adhesives and resin composites), and the specimens were assessed using an SBS test. The failure mode was examined using a stereomicroscope. The SBS data were evaluated using a three-way ANOVA and a Tukey post hoc test. The SBS were significantly affected by the RMCs, mouthwashes, and surface treatment protocols. Both surface treatment protocols (HF and SB) for both RMCs, whether immersed in anti-COVID-19 mouthwash or not, improved the SBS. For the VE immersed in HP and PVP-I, the HF surface treatment had the highest SBS. For the ShB immersed in HP and PVP-I, the SB surface treatment had the highest SBS.

Corona Virus Disease 2019 (COVID-19) is a new strain of coronavirus called SARS-CoV-2, which was identified in Wuhan, China, in December 2019. The rapid transmission of COVID-19 from human to human forced researchers to find a potent drug by setting aside the time-consuming traditional method in drug development. The molecular docking approach is one a reliable method to screening compound from chemical drug or by finding a compound from Indonesian herbal plants. The present study aimed to assess the potency of compounds from five medicinal plants as potential inhibitors of PLpro and 3CLpro from SARS-CoV-2 using molecular study. The molecular docking was performed using Protein-Ligand Ant System (PLANTS) to analyze the potential compounds by the docking score. Remdesivir triphosphate was used as a standard for the comparison of the test compounds. The docking score obtained from the docking of PLpro with native ligand, remdesivir triphosphate, curcumin, demethoxycurcumin, bisdemethoxycurcumin, luteolin, apigenin, quercetin, kaempferol, formononetin-7-O-glucuronide, andrographolide, and neoandrographolide were -111.441, -103.827, -103.609, -102.363, -100.27, -79.6655, -78.6901, -80.9337, -79.4686, -82.1124, -79.1789, and -97.2452, respectively. Meanwhile, docking score with 3CLpro for the same ligand were -64.0074, -86.1811, -81.428, -87.1625, -78.2899, -73.4345, -70.3368, -71.5539, -68.4321, -72.0154, -75.9777, and -93.7746. The docking score data suggest that curcumin was the most potential as a PLpro inhibitor, while neoandrographolide was the best as a 3CLpro inhibitor.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic.

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 and became a pandemic in a critically short time. Phenolic secondary metabolites attracted much attention from the pharmaceutical industries for their easily accessible natural sources and proven antiviral activity. In our mission, a metabolomics study of the Garcinia cambogia Roxb. fruit rind was performed using LC-HRESIMS to investigate its chemical profile, especially the polar aspects, followed by a detailed phytochemical analysis, which led to the isolation of eight known compounds. Using spectrometric techniques, the isolated compounds were identified as quercetin, amentoflavone, vitexin, rutin, naringin, catechin, p-coumaric, and gallic acids. The antiviral activities of the isolated compounds were investigated using two assays; the 3CL-Mpro enzyme showed that naringin had a potent effect with IC50 16.62 μg/mL, followed by catechin and gallic acid (IC50 26.2, 30.35 μg/mL, respectively), while the direct antiviral inhibition effect of naringin confirmed the potency with an EC50 of 0.0169 μM. To show the molecular interaction, in situ molecular docking was carried out using a COVID-19 protease enzyme. Both biological effects and docking studies showed the hydrophobic interactions with Gln 189 or Glu 166, per the predicated binding pose of the isolated naringin.

SARS-CoV-2 is the latest worldwide pandemic declared by the World Health Organization and there is no established anti-COVID-19 drug to combat this notorious situation except some recently approved vaccines. By affecting the global public health sector, this viral infection has created a disastrous situation associated with high morbidity and mortality rates along with remarkable cases of hospitalization because of its tendency to be high infective. These challenges forced researchers and leading pharmaceutical companies to find and develop cures for this novel strain of coronavirus. Besides, plants have a proven history of being notable wellsprings of potential drugs, including antiviral, antibacterial, and anticancer therapies. As a continuation of this approach, plant-based preparations and bioactive metabolites along with a notable number of traditional medicines, bioactive phytochemicals, traditional Chinese medicines, nutraceuticals, Ayurvedic preparations, and other plant-based products are being explored as possible therapeutics against COVID-19. Moreover, the unavailability of effective medicines against COVID-19 has driven researchers and members of the pharmaceutical, herbal, and related industries to conduct extensive investigations of plant-based products, especially those that have already shown antiviral properties. Even the recent invention of several vaccines has not eliminated doubts about safety and efficacy. As a consequence, many limited, unregulated clinical trials involving conventional mono- and poly-herbal therapies are being conducted in various areas of the world. Of the many clinical trials to establish such agents as credentialed sources of anti-COVID-19 medications, only a few have reached the landmark of completion. In this review, we have highlighted and focused on plant-based anti-COVID-19 clinical trials found in several scientific and authenticated databases. The aim is to allow researchers and innovators to identify promising and prospective anti-COVID-19 agents in clinical trials (either completed or recruiting) to establish them as novel therapies to address this unwanted pandemic. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) outbreak has presented enormous challenges for healthcare, societal, and economic systems worldwide. There is an urgent global need for a universal vaccine to cover all SARS-CoV-2 mutant strains to stop the current COVID-19 pandemic and the threat of an inevitable second wave of coronavirus. Carbon dioxide is safe and superior antimicrobial, which suggests it should be effective against coronaviruses and mutants thereof. Depending on the therapeutic regime, CO2 could also ameliorate other COVID-19 symptoms as it has also been reported to have antioxidant, anti-inflammation, anti-cytokine effects, and to stimulate the human immune system. Moreover, CO2 has beneficial effects on respiratory physiology, cardiovascular health, and human nervous systems. This article reviews the rationale of early treatment by inhaling safe doses of warmed humidified CO2 gas, either alone or as a carrier gas to deliver other inhaled drugs may help save lives by suppressing SARS-CoV-2 infections and excessive inflammatory responses. We suggest testing this somewhat counter-intuitive, but low tech and safe intervention for its suitability as a preventive measure and treatment against COVID-19. Overall, development and evaluation of this therapy now may provide a safe and economical tool for use not only during the current pandemic but also for any future outbreaks of respiratory diseases and related conditions.

Aim: To investigate the prospective anti COVID-19 activity of Egyptian propolis. Material & methods: Propolis samples were collected from different Egyptian geographical areas and characterized using standardized methods, scanning electron microscope and gas chromatography/mass spectrometry along with computational modeling to predict the anti-COVID-19 activity. Results & conclusion: Gas chromatography/mass spectrometry analysis of Menoufia propolis proved the presence of Octatriacontyl pentafluoropropionate (4.2%). Docking analyses declared that Octatriacontyl pentafluoropropionate is well oriented inside the enzyme pockets, in addition to excellent binding manner with the active site of the target macromolecules (RNA-dependent RNA polymerase, Spike protein S1 and main protease) in relation to some broad-spectrum antiviral agents. Menoufia propolis could be a promising candidate in the combat against the pandemic COVID-19. [ABSTRACT FROM AUTHOR]

The current struggle to control and contain COVID-19 is critical and surgeons are on the front line in the fight against this virus. Surgeons, and other medical workers in the field of surgery, have a solid foundation and experience in medical treatment and intensive care, and an understanding of the support of respiratory, circulatory, digestive, and other systemic organs. Furthermore, the operative standards of aseptic technique in their daily work enable surgeons to adapt to the working environment in infected areas. As surgeons in the anti-pandemic front line in China, we describe our experience with the diagnosis and treatment of COVID-19 in this country and how the work of surgeons is unfolding during the pandemic. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

In this paper, we studied the in silico interaction of angiotensin-converting enzyme 2 (ACE2) human receptor with two bioactive compounds, i.e., nicotine and caffeine, via molecular dynamic (MD) simulations. The simulations reveal the efficient blocking of ACE2 by caffeine and nicotine in the exposure to the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have selected the two most important active sites of ACE2-S protein, i.e., 6LZG and 6VW1, which are critically responsible in the interaction of S protein to the receptor and thus, we investigated their interaction with nicotine and caffeine through MD simulations. Caffeine and nicotine are interesting structures for interactions because of their similar structure to the candidate antiviral drugs. Our results reveal that caffeine or nicotine in a specific molar ratio to 6LZG shows a very strong interaction and indicate that caffeine is more efficient in the interaction with 6LZG and further blocking of this site against S protein binding. Further, we investigated the interaction of ACE2 receptor- S protein with nicotine or caffeine when mixed with candidate or approved antiviral drugs for SARS-CoV-2 therapy. Our MD simulations suggest that the combination of caffeine with ribavirin shows a stronger interaction with 6VW1, while in case of favipiravir+nicotine, 6LZG shows potent efficacy of these interaction, proposing the potent efficacy of these combinations for blocking ACE2 receptor against SARS-CoV-2.

Due to inadequate pharmaceutical wastewater treatment, anticancer contaminants from the pharmaceutical industry frequently end up in the aquatic environment where they endanger aquatic life and humans. As a result, the appropriate treatment of wastewater that contains anticancer agents is crucial for pollution prevention. The purpose of this work is to assess the effectiveness of a Fe 3 O 4 @ZIF-8 nanocomposite as an adsorbent to remove of the chemotherapeutic drugs doxorubicin (DOX) from aqueous solution. SEM, XRD, BET, FT-IR, Zeta potential, and point of zero charge analysis were used to study the surface and structural characteristics of the Fe 3 O 4 @ZIF-8 nanocomposite. Via the proposed treatment, 804.84 mg/g elimination was successful under the following circumstances: pH = 6; Fe 3 O 4 @ZIF-8 dose = 0.02 g/25 mL; DOX concentration = 1.22x10 -3  mol; adsorption time = 100 min; and shaking speed = 200 rpm. A investigation of isotherms shown that the Langmuir equation and experimental data suited each other quite well. The adsorption of DOX on Fe 3 O 4 @ZIF-8 was endothermic and spontaneous, in accordance with thermodynamic properties. Furthermore, the elimination of DOX was enhanced by the rise in solution temperature. The kinetic analysis revealed that the pseudo-second order was fitted by the model. The suggested adsorption method could recycle Fe 3 O 4 @ZIF-8 nanocomposite six times, with a modest reduction in its ability for adsorption. For all XRD reflection peaks, physical characteristics including strain rates were computed and the dislocation of was 4.7 × 10 -6 . Investigate the activity of the DOX towards COVID-19, breast and prostate cancer using molecular docking.

VV116 is an oral nucleoside anti-COVID-19 drug undergoing clinical trials in China. We aimed to characterize its metabolites in plasma, urine, and feces of healthy Chinese male subjects after a single oral administration of 400 mg VV116, by using UHPLC-UV-Orbitrap-MS. After oral administration, VV116 was almost completely converted into the metabolite 116-N1. Seventeen other metabolites produced by the subsequent metabolism of 116-N1 were also detected, including 6 phase I metabolites and 11 phase II metabolites resulting from hydrolysis, oxidative deamination, oxidation, and CN-group removal and conjugations. The results were exploratory. The major metabolite of VV116 in human plasma and urine was 116-N1, the main metabolites in feces were M2 and 116-N1. We then synthesized a reference M2 standard and confirmed its structure by MS and NMR. • Characterization of 18 metabolites in humans of VV116 by HRMS. • Structure confirmation of major metabolite M2 by NMR. [ABSTRACT FROM AUTHOR]

Edible mushrooms are ubiquitous around the world due to their enormous health benefits. Mushrooms have been used as folk medicine and healthy food from ancient times but their health-promoting effects have not been explored. As a superfood, mushroom powder is an essential component of the human diet for improving health and immunity. Bioactive components present in them such as proteins, polysaccharides, terpenes, and lipids have recently sparked much attention to exhibit therapeutic properties such as anti-cancer, immunomodulatory, anti-hypercholesterolemia, antiviral, antidiabetic, and anti-inflammatory effects. Moreover, these isolated compounds have the potentiality to be used in dietary supplements and medicines. In addition, numerous bioactive compounds such as ergosterol, gallic acid, and cordycepin proved to be essential in preventing or reducing the severity of COVID-19. This review unveils a comprehensive understanding of the nutraceutical as well as the medicinal potential of mushrooms and their applications in food products for human wellness. [ABSTRACT FROM AUTHOR]

In preceding years, bioactive peptides (BAPs) have piqued escalating attention owing to their multitudinous biological features. To date, many potential BAPs exhibiting anti-cancer activities have been documented; yet, obstacles such as their safety profiles and consumer acceptance continue to exist. Moreover, BAPs have been discovered to facilitate the suppression of Coronavirus Disease 2019 (CoVID-19) and maybe ideal for treating the CoVID-19 infection, as stated by published experimental findings, but their widespread knowledge is scarce. Likewise, there is a cornucopia of BAPs possessing neuroprotective effects that mend neurodegenerative diseases (NDs) by regulating gut microbiota, but they remain a subject of research interest. Additionally, a plethora of researchers have attempted next-generation approaches based on BAPs, but they need scientific attention. The text format of this critical review is organized around an overview of BAPs' versatility and diverse bio functionalities with emphasis on recent developments and novelties. The review is alienated into independent sections, which are related to either BAPs based disease management strategies or next-generation BAPs based approaches. BAPs based anti-cancer, anti-CoVID-19, and neuroprotective strategies have been explored, which may offer insights that could help the researchers and industries to find an alternate regimen against the three aforementioned fatal diseases. To the best of our knowledge, this is the first review that has systematically discussed the next-generation approaches in BAP research. Furthermore, it can be concluded that the BAPs may be optimal for the management of cancer, CoVID-19, and NDs; nevertheless, experimental and preclinical studies are crucial to validate their therapeutic benefits. [Display omitted] [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a serious global healthcare crisis, so there is an emergence of identifying efficacious therapeutic options. In a setting where there is an unavailability of definitive medication along with the constant eruption of vaccine-related controversies, the drug-repositioning approach seems to be an ideal step for the management of COVID-19 patients. Fluoroquinolones (FQs) are commonly prescribed antibiotics for the treatment of genitourinary tract and upper respiratory tract infections, including severe community-acquired pneumonia. Research over the years has postulated multifaceted implications of FQs in various pathological conditions. Previously, it has been reported that few, but not all FQs, possess strong antiviral activity with an unknown mechanism of action. Herein, an interesting perspective is discussed on repositioning possibilities of FQs for the SARS-CoV-2 infections based on the recent in silico evidential support. Noteworthy, FQs possess immunomodulatory and bactericidal activity which could be valuable for patients dealing with COVID-19 related complications. Conclusively, the current perspective could pave the way to initiate pre-clinical testing of FQs against several strains of SARS-CoV-2., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The representative anti-COVID-19 herbs, i.e., Poriacocos, Pogostemon, Prunus, and Glycyrrhiza plants, are commonly used in the prevention and treatment of COVID-19, a pandemic caused by SARSCoV- 2. Diverse medicinal compounds with favorable anti-COVID-19 activities are abundant in these plants, and their unique pharmacological/pharmacokinetic properties have been revealed. However, the current trends in Drug Metabolism/Pharmacokinetic (DMPK) investigations of anti-COVID-19 herbs have not been systematically summarized., Methods: In this study, the latest awareness, as well as the perception gaps regarding DMPK attributes, in the anti- COVID-19 drug development and clinical usage was critically examined and discussed., Results: The extracts and compounds of P.cocos, Pogostemon, Prunus, and Glycyrrhiza plants show distinct and diverse absorption, distribution, metabolism, excretion, and toxicity (ADME/T) properties. The complicated herbherb interactions (HHIs) and herb-drug interactions (HDIs) of anti-COVID-19 Traditional Chinese Medicine (TCM) herb pair/formula dramatically influence the PK/pharmacodynamic (PD) performance of compounds thereof, which may inspire researchers to design innovative herbal/compound formulas for optimizing the therapeutic outcome of COVID-19 and related epidemic diseases. The ADME/T of some abundant compounds in anti-COVID-19 plants have been elucidated, but DMPK studies should be extended to more compounds of different medicinal parts, species, and formulations and would be facilitated by various omics platforms and computational analyses., Conclusion: In the framework of pharmacology and pharmacophylogeny, the DMPK knowledge base would promote the translation of bench findings into the clinical practice of anti-COVID-19 and speed up the anti-COVID-19 drug discovery and development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic fatal infection with no known treatment. The severity of the disease and the fast viral mutations forced the scientific community to search for potential solution. Here in the present manuscript, some benzofused1,2,3triazolesulfonamide hybrids were synthesized and evaluated for their anti- SARS-CoV-2 activity using in silico prediction then the most potent compounds were assessed using in-Vitro analysis. The in-Silico study was assessed against RNA dependent RNA polymerase, Spike protein S1, Main protease (3CLpro) and 2′-O-methyltransferase (nsp16). It was found that 4b and 4c showed high binding scores against RNA dependent RNA polymerase reached −8.40 and −8.75 ​kcal/mol, respectively compared to the approved antiviral (remdesivir −6.77 ​kcal/mol). Upon testing the binding score with SARS-CoV-2 Spike protein it was revealed that 4c exhibited the highest score (−7.22 ​kcal/mol) compared to the reference antibacterial drug Ceftazidime (−6.36 ​kcal/mol). Surprisingly, the two compounds 4b and 4c showed the highest binding scores against SARS-CoV-2 3CLpro (−8.75, −8.48 ​kcal/mol, respectively) and nsp16 (- 8.84 and – 8.89 ​kcal/mol, respectively) displaying many types of interaction with all the enzymes binding sites. The derivatives 4b and 4c were examined in vitro for their potential anti-SARS-CoV-2 and it was revealed that 4c was the most promising compound with IC50 reached 758.8108 ​mM and complete (100%) inhibition of the binding of SARS-CoV-2 virus to human ACE2 can be accomplished by using 0.01 ​mg. • This is the first work to predict the anti-COVID-19 activity of some benzofused 1,2,3-triazolesulfonamide hybrids. • The synthesized compounds were tested against several viral enzymes including 2′-O-methyltransferase (nsp16). • 4c was the most promising compound with 100% inhibition of the binding of SARS-CoV-2 virus to human ACE2 upon using 0.01 ​mg. [ABSTRACT FROM AUTHOR]

Pomegranate peel, the waste product generated from pomegranate fruit, has prophylactic properties, such as antimicrobial, anti-malarial, and controls respiratory infections and influenza. Based on the previous literature and need of the hour, molecular docking was performed to evaluate the inhibitory effects of major pomegranate peel polyphenols against COVID-19. Among the 44 studied compounds, 37 polyphenols show interaction with the catalytic dyad of the M pro protease and 18 polyphenols have a higher binding affinity than that of the M pro protease inhibitor (N3), indicating their high probability of binding at ACE2: SARS-CoV-2 interface. Furthermore, several polyphenols studied in this work are found to have higher binding affinity as compared to those of hydroxychloroquine, lopinavir, nelfinavir, and curcumin, some of which have been earlier tested against COVID-19. Further, molecular dynamics simulations (200 ns) for M pro -polyphenols including pelargonidin3-glucoside, quercetin3-O-rhamnoside, cyanidin3-glucoside and punicalin revealed highly stable complexes with less conformational fluctuations and similar degree of compactness. Estimation of total number of intermolecular hydrogen bonds and binding free energy confirmed the stability of these M pro -polyphenol complexes over M pro -curcumin complex. Based on the greater binding affinity of polyphenols of pomegranate peel towards M pro as compared to that of curcumin, pomegranate peel may be considered in any herbal medicinal formulation or may be incorporated into daily diets for prevention of COVID-19.Communicated by Ramaswamy H. Sarma.

In this paper, we studied the in silico interaction of angiotensin-converting enzyme 2 (ACE2) human receptor with two bioactive compounds, i.e., nicotine and caffeine, via molecular dynamic (MD) simulations. The simulations reveal the efficient blocking of ACE2 by caffeine and nicotine in the exposure to the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have selected the two most important active sites of ACE2-S protein, i.e., 6LZG and 6VW1, which are critically responsible in the interaction of S protein to the receptor and thus, we investigated their interaction with nicotine and caffeine through MD simulations. Caffeine and nicotine are interesting structures for interactions because of their similar structure to the candidate antiviral drugs. Our results reveal that caffeine or nicotine in a specific molar ratio to 6LZG shows a very strong interaction and indicate that caffeine is more efficient in the interaction with 6LZG and further blocking of this site against S protein binding. Further, we investigated the interaction of ACE2 receptor- S protein with nicotine or caffeine when mixed with candidate or approved antiviral drugs for SARS-CoV-2 therapy. Our MD simulations suggest that the combination of caffeine with ribavirin shows a stronger interaction with 6VW1, while in case of favipiravir+nicotine, 6LZG shows potent efficacy of these interaction, proposing the potent efficacy of these combinations for blocking ACE2 receptor against SARS-CoV-2. [ABSTRACT FROM AUTHOR]