Antiviral activitiy of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds of Curcuma longa against NSP3 on SARS-CoV-2

SARS-CoV-2 genome encodes two large polyproteins (pp), pp1a and pp1ab which are cleaved and transformed into a mature form by a protease, non-structural protein 3 (NSP3). NSP3 is encoded by open reading frame (ORF) 1a/b. Curcuma longa (C. longa) or turmeric has been documented to have antiviral effects. The aim of this study was to assess the viral activities of C. longa against SARS-CoV-2 focusing on its potency to inhibit viral replication by targeting NSP3. PubChem databases were used to obtain the metabolic profile of C. longa. The compound's interaction with nucleocapsid was analyzed using molecular docking with Molegro Virtual Docker. Bioinformatics analysis based on rerank score presents all compounds of C. longa have higher binding affinity than the native ligand with cyclocurcumin as the lowest score (-128.38 kcal/mol). This anti-viral activity was hypothesized from the similarity of hydrogen bonds with amino acid residues Ser 128 and Asn 40 as key residues present in Ribavirin. This study reveals that C. longa is the potential to be developed as an antiviral agent through replication inhibition in SARS-CoV-2 targeting its replication mediated by NSP3.

Studying the Predictive Effects of Bacterial Carotenoids in the Treatment of Endometriosis Using Virtual Screening Methods

Background: Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. Cytokines appear to play vital roles in the development and progression of endometriosis and associated infertility. Tumor necrosis factoralpha (TNF-alpha) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. TNF- alpha plays an important role in endometrial physiology as well as during early implantation. In addition, this cytokine has a considerable pathophysiological function in diseases such as menorrhagia, endometriosis, or infertility due to its regulatory impact on proliferation, differentiation, and angiogenesis in the human endometrium. In women with endometriosis, TNF-alpha levels increases in peritoneal fluid and serum significantly. In the present study, we focused on finding novel small molecules that can directly block TNFalpha- hTNFR1 (human TNF receptor 1) interaction. Method(s): In this regard, TNF-alpha inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-alpha-hTNFR1 interaction with the help of a combination of in silico approaches, based on virtual screening, molecular docking, and molecular dynamics (MD) simulation. Result(s): A total of 125 carotenoids were selected out of 1204 natural molecules, based on their pharmacokinetics properties, and they all met Lipinski's rule of five. Among them, sorgomol, strigol, and orobanchol had the most favorable DELTAG with the best pharmacokinetics properties and were selected for MD simulation studies, which explored the complex stability and the impact of ligands on protein conformation. It was shown that sorgomol formed the most hydrogen bonds, resulting in the highest binding energy with the lowest RMSD and RMSF. Conclusion(s): Our results showed that sorgomol was the most appropriate candidate as a TNF-alpha inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-alpha which plays an important role in the inflammation of endometriosis.

In silico screening of chalcones and their derivatives as potential inhibitors of spike proteins and ACE2 enzymes for SARS-CoV-2 treatment

The COVID-19 pandemic causing acute respiratory syndrome is a significant public health problem. Drugs that can treat this disease are currently a high priority. The SARS-CoV-2 spike protein and human ACE2 enzyme receptor, which both play important roles in virus entry into the host cell, are promising therapeutic targets for inhibiting viral infection. This research evaluates the potential of chalcone compounds to inhibit the spike proteins and ACE2 enzymes through molecular docking in silico approaches. Based on the ChemFaces database, we collected 92 chalcone compounds. These compounds were further docked to target the active sites of spike protein and human ACE2. After comparing the binding energies of the 92 compounds to artemisinin, ribavirin, and lopinavir, which have inhibitory activity to these protein targets of SARS-CoV-2, we chose 20 out of the 92 compounds that had a higher ability to inhibit the protein targets than the reference inhibitors. Next, five phytochemical compounds with the best binding energy were selected, which included flavanomarein, sarcandrone B, sarcandrone A, calyxin H, and sieboldin. Then, Lipinski's 5 rule was used to evaluate the druglike properties of these compounds. Predictive ADME/tox filtering tests were also applied to the top docked compounds. The results suggest that sarcandrone B has good pharmacokinetic properties, which should be further explored as an anti-SARS-CoV-2. To confirm these findings, experimental studies are recommended.

Potential Health Survey of Traditional Spices & Herbs in Prevention and Treatment of COVID-19: A Review

The coronavirus (COVID-19) is a global public health pandemic disease emerged from the novel strain of the coronavirus 2 (SARS-CoV-2) that caused severe acute respiratory syndrome. It is the most significant respiratory illness that has affected the world since World War II. Currently, there is no globally approved drug for the treatment of pandemic COVID-19 except for some recently approved vaccines. Instead, various non-specific treatment options are being utilized by different countries. While some of these are effective, there is a lack of well-documented studies on the impact of traditional medicines on the management of SARS-CoV-2 in vitro and in silico. For thousands of years, traditional healers have been using various herbs and spices products and dietary plants to treat various diseases. This review aims to provide information on the use of traditional spices & herbs in COVID-19 protection and treatment and present the main characteristics of these products and their potential antiviral actions. Various databases were searched for articles related to the use of various herbs for the treatment of viral infections. Many of these studies show that various plant compounds can be utilized for the treatment of viral infections. This study aims to summarize the common used of herbal products and dietary supplements with potent bioactive compounds in treatment or prevent of COVID-19.

Efficacy evaluation of quercetin and its analogues on the main protease enzyme of the COVID-19 using molecular docking studies

Introduction: COVID-19 is an acute respiratory infectious disease caused by the SARS-CoV-2 virus. There is an urgent need to discover antiviral drugs for better performance against new strains of coronaviruses (CoVs) due to the rapid spread of the disease despite scientific advances in vaccine development. This study aimed to evaluate the efficacy of quercetin and its analogues on the COVID-19 Mpro enzyme. Material & Methods: In this descriptive-analytical study, the three-dimensional structures of quercetin analogues (20 compounds), standard drugs (ritonavir and lopinavir), and the COVID-19 Mpro enzyme were obtained from PubChem and PDB databases for bioinformatics study, respectively. Molecular docking studies of the compounds on theMpro were performed using MOE-2014 software. Afterward, the physicochemical properties and biological activity of the compounds were predicted using Swiss ADME, PASS, and Swiss Target Prediction software. Findings: The findings of the present study showed that the most important bonds involved in drug-receptor binding are hydrogen, hydrophobic, and - interaction bonds. The best docking results were obtained for Baicalein, Genistein, Naringenin, and Quercetin compounds with strong binding energy (-12.83 to -13.54 kcal/mol), compared to ritonavir and lopinavir. These compounds have a greater tendency to bind to the catalytic amino acids His41 and Cys145 and other key amino acids of the active site of the COVID-19 Mpro enzyme. Discussion & Conclusion: Based on the results of bioinformatics studies, quercetin analogues had more effective inhibition than standard chemical drugs due to their suitable placement in the active site of the main protease enzyme of COVID-19 and can be good candidates for in vitro and in vivo studies.

The Suggestion of a Drug for COVID-19 with Molecular Docking

Background and objectives: This study aimed to study the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) spike protein complex and seven drugs that inhibit the angiotensin-converting enzyme 2. Methods: Plots of protein-ligand interaction were obtained using the LigPlot software. In addition, binding energies in kcal/mol, hydrophobic interactions, and hydrogen bonds were determined. Autodock software v.1.5.6 and AutoDock Vina were used for the analysis of molecular docking processes. Results: The only structure that interacted with the SARS‑CoV‑2 spike protein was anakinra. Conclusion: Anakinra was the only drug that interacted with the SARS‑CoV‑2 spike protein. This could be further investigated for finding a temporary alternative medicine for the treatment of coronavirus disease 2019. [ABSTRACT FROM AUTHOR] Copyright of Medical Laboratory Journal is the property of Golestan University of Medical Sciences, Deputy of Research & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Studies towards investigation of Naphthoquinone-based scaffold with crystal structure as lead for SARS-CoV-19 management.

In this work, 1-(4-bromophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-3,8­dione (1-(4-BP)DHCBN-3,8-D) has been characterized by single crystal X-ray to get it's crystal structure with R(all data) - R1 = 0.0569, wR2 = 0.0824, 13C and 1HNMR, as well as UV-Vis and IR spectroscopy. Quantum chemical calculations via DFT were used to predict the compound structural, electronic, and vibrational properties. The molecular geometry of 1-(4-BP)DHCBN-3,8-Dwas optimized utilizing the B3LYP functional at the 6-311++G(d,p) level of theory. The Infrared spectrum has been recorded in the range of 4000-550 cm-1. The Potential Energy Distribution (PED) assignments of the vibrational modes were used to determine the geometrical dimensions, energies, and wavenumbers, and to assign basic vibrations. The UV-Vis spectra of the titled compound were recorded in the range of 200-800 nm in ACN and DMSO solvents. Additionally, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap and electronic transitions were determined using TD-DFT calculations, which also simulate the UV-Vis absorption spectrum. Natural Bond Orbital (NBO) analysis can be used to investigate electronic interactions and transfer reactions between donor and acceptor molecules. Temperature-dependent thermodynamic properties were also calculated. To identify the interactions in the crystal structure, Hirshfeld Surface Analysis was also assessed. The Molecular Electrostatic Potential (MEP) and Fukui functions were used to determine the nucleophilic and electrophilic sites. Additionally, the biological activities of 1-(4-BP)DHCBN-3,8-D were done using molecular docking. These results demonstrate a significant therapeutic potential for 1-(4-BP)DHCBN-3,8-D in the management of Covid-19 disorders. Molecular Dynamics Simulation was used to look at the stability of biomolecules.

Ligand-based discovery of coronavirus main protease inhibitors using MACAW molecular embeddings

Ligand-based drug design methods are thought to require large experimental datasets to become useful for virtual screening. In this work, we propose a computational strategy to design novel inhibitors of coronavirus main protease, M(pro). The pipeline integrates publicly available screening and binding affinity data in a two-stage machine-learning model using the recent MACAW embeddings. Once trained, the model can be deployed to rapidly screen large libraries of molecules in silico. Several hundred thousand compounds were virtually screened and 10 of them were selected for experimental testing. From these 10 compounds, 8 showed a clear inhibitory effect on recombinant M(pro), with half-maximal inhibitory concentration values (IC(50)) in the range 0.18-18.82 μM. Cellular assays were also conducted to evaluate cytotoxic, haemolytic, and antiviral properties. A promising lead compound against coronavirus M(pro) was identified with dose-dependent inhibition of virus infectivity and minimal toxicity on human MRC-5 cells.

Computational approaches to define poncirin from Magnolia champaka leaves as a novel multi-target inhibitor of SARS-CoV-2.

Phytochemical-based drug discovery against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been the focus of the current scenario. In this context, we aimed to perform the phytochemical profiling of Magnolia champaka, an evergreen tree from the Magnoliaceae family, in order to perform a virtual screening of its phytoconstituents against different biological targets of SARS-CoV-2. The phytochemicals identified from the ethanol extract of M. champaka leaves using liquid chromatography-mass spectroscopy (LC-MS) technique were screened against SARS-CoV-2 spike glycoprotein (PDB ID: 6M0J), main protease/Mpro (PDB ID: 6LU7), and papain-like protease/PLpro (PDB ID: 7CMD) through computational tools. The experimentation design included molecular docking simulation, molecular dynamics simulation, and binding free energy calculations. Through molecular docking simulation, we identified poncirin as a common potential inhibitor of all the above-mentioned target proteins. In addition, molecular dynamics simulations, binding free energy calculations, and PCA analysis also supported the outcomes of the virtual screening. By the virtue of all the in silico results obtained, poncirin could be taken for in vitro and in vivo studies in near future.Communicated by Ramaswamy H. Sarma.

Structure-based virtual screening and molecular docking of drugs against the SARS-CoV-2 spike protein-ACE2 receptor complex

The agent responsible for the COVID-19 pandemic was the newly discovered coronavirus SARS-CoV-2. A trimeric spike protein on the SARS-CoV-2 virion binds to the ACE2 receptor on host cells. In this study we performed a structure-based virtual screening and molecular docking of existing drugs against a high-resolution structure of the SARS-CoV-2 spike protein-ACE2 receptor complex. The 2.5-A crystal structure of the C-terminal domain of the SARS-CoV-2 spike protein (residues 319-541) in complex with human ACE2 (SARS-CoV-2-S-CTD/hACE2) (PDB ID: 6LZG) was used as the target for screening 4,374 FDA-approved drugs from the ZINC15 database using PyRx software. Molecular docking was performed using BIO VIA Discovery Studio Visualizer. The top twenty highest affinity drugs had binding energies of -7.0 to -8.8 kcal/mol. The highest affinity drug was the selective vasopressin V2-receptor antagonist Tolvaptan, for which molecular docking identified drug-amino acid residue interactions with ACE2. Other drugs displaying binding energies better than -8.0 kcal/mol were Nizoral, Amaryl, Accolate, Sorafenib, Glipizide and Azelastine. The predicted interactions of these highest affinity drugs with residues in ACE2 were at positions that could disrupt the spike protein-ACE2 complex, so these drugs have the potential to be repurposed as inhibitors of the SARS-CoV-2 virus.

Systematic structure guided clustering of chemical lead compounds targeting RdRp of SARS-CoV-2

BACKGROUND: To combat the global health issue caused by SARS-CoV2, scientists are attempting various therapeutic approaches towards drug discovery including computational biology and drug-repurposing. Recent studies have highlighted the conserved nature of RNA-dependent RNA polymerase (RdRp) of coronaviruses affecting human, bat and animals. In this study attempts have been made to identify the potential inhibitors of RdRp by utilizing molecular docking and MD simulation studies. METHOD(S): Systematic structure-based screening of chemical compounds from public libraries was performed to identify the potential lead molecules inhibiting RdRp. This structure driven clustering of compounds is based on decision tree model generated by combining two properties: 1) shape descriptors;and 2) critical number of multiple bonds. The enabled screening of potential chemical compounds was subjected to molecular docking followed by molecular dynamics simulation studies. RESULT(S): The results revealed that the stability of protein-drug complex structure was in the order of RdRp-Oxoglaucine >RdRp-Flutroline >RdRp-Brucine complex. CONCLUSION(S): This study identifies Oxoglaucine, Brucine and Flutroline as prospective inhibiting agents of SARS-CoV-2 RdRp and further warrants for experimental validation. Copyright © 2022 EDIZIONI MINERVA MEDICA.

Synthesis, characterization, theoretical study and molecular docking studies of some new cobalt(II), chromium(II) and nickel (II) complexes

Three transition metal complexes with general formula [M(L)(2)] (Co = (1), Cr = (2) and Ni = (3)), were synthesized by treating CoCl2/CrCl3 center dot 6H(2)O/NiCl2 center dot 6H(2)O with an ONS-donor Schiff base ligand (HL) derived from the condensation of 3,5-Diiodosalicylaldehyde and 4,4-Dimethyl-3-thiosemicarbazide. The geometry around the centre metal ions was octahedral as revealed by the data collection from spectroscopic studies. The newly synthesized compounds were fully characterized by various physicochemical and spectroscopic methods. DFT calculations were performed on the compounds to get a structure-property relationship. Some global reactivity descriptors like chemical potential (mu), electronegativity (chi), hardness (eta) and electrophilicity index (omega) were also evaluated using DFT method. The ADMET prediction analyses have been explored. Molecular dynamics simulations were also studied. Besides this, to find a potential inhibitor for anti-SARS-CoV-2, metal complexes are also assessed through molecular docking and 3-D visualizations of intermolecular interactions against main protease (M-pro) of SARS-CoV-2 (PDB ID: 7JKV). The molecular docking calculations of the complex (1) into the main protease of SARS-CoV-2 virus (PDB ID: 7JKV) revealed the binding energy of -7.2 kcal/mol with an inhibition constant of 2.529 mu M at inhibition binding site of receptor protein. Complex (2) with SARS-CoV-2 resulted in the binding energy of -7.8 kcal/mol and the inhibition constant of 5.231 mu M. Similarly, complex (3) with SARS-CoV-2 (PDB ID: 7JKV) exhibited the binding energy and the inhibition constant of -7.5 kcal/mol and 3.585 mu M respectively at inhibition binding site of receptor protein. Overall, in silico studies explored the potential role of metal complexes, which would offer new drug candidates against SARS-CoV-2.

An in silico study on inhibitability of Baloxavir marboxil, Baricitinib, Galidesivir, Nitazoxanide, and Oseltamivir against SARS-CoV-2

Baloxavir marboxil (D1), Baricitinib (D2), Galidesivir (D3), Nitazoxanide (D4), and Oseltamivir (D5) are well-known performing broad-spectrum activity against a variety of viruses, thus holding high potentiality towards SARS-CoV-2. Quantum properties were examined using density functional theory (DFT). The inhibitability of the drugs towards Angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 main protease (6LU7) was evaluated by molecular docking simulation, while their bio-compatibility was justified by physicochemical properties obtained from QSARIS-based analysis in reference to Lipinski's rule of five. Quantum analysis suggests that the compounds are highly favourable for intermolecular interaction towards protein structures. Given ligand-ACE2 systems, the inhibitory effectiveness follows the order D3-ACE2?>?D4-ACE2?>?D2-ACE2?>?D5-ACE2?>?D1-ACE2;and the corresponding order for ligand-6LU7 systems is D2-6LU7?>?D4-6LU7?>?D3-6LU7?>?D5-6LU7?>?D1-6LU7. Galidesivir is predicted as the most effective inhibitor towards both targeted protein structures (DSaverage -13.1 kcal.mol-1) and the most bio-compatible molecule (Mass 264.9 amu;LogP -0.9;Polarisability 26.8 Å3). The theoretical screening suggests all drugs, especially Galidesivir (D3), promising for treatment of SARS-CoV-2 infection and encourages in-related clinical trials.

Integrated bioinformatics-cheminformatics approach toward locating pseudo-potential antiviral marine alkaloids against SARS-CoV-2-Mpro.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with the most contagious variants, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and Omicron (B.1.1.529) has continuously added a higher number of morbidity and mortality, globally. The present integrated bioinformatics-cheminformatics approach was employed to locate potent antiviral marine alkaloids that could be used against SARS-CoV-2. Initially, 57 antiviral marine alkaloids and two repurposing drugs were selected from an extensive literature review. Then, the putative target enzyme SARS-CoV-2 main protease (SARS-CoV-2-Mpro) was retrieved from the protein data bank and carried out a virtual screening-cum-molecular docking study with all candidates using PyRx 0.8 and AutoDock 4.2 software. Further, the molecular dynamics (MD) simulation of the two most potential alkaloids and a drug docking complex at 100 ns (with two ligand topology files from PRODRG and ATB server, separately), the molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy, and contributions of entropy were investigated. Then, the physicochemical-toxicity-pharmacokinetics-drug-likeness profiles, the frontier molecular orbitals energies (highest occupied molecular orbital, lowest unoccupied molecular orbital, and ΔE), and structural-activity relationship were assessed and analyzed. Based on binding energy, 8-hydroxymanzamine (-10.5 kcal/mol) and manzamine A (-10.1 kcal/mol) from all alkaloids with darunavir (-7.9 kcal/mol) and lopinavir (-7.4 kcal/mol) against SARS-CoV-2-Mpro were recorded. The MD simulation (RMSD, RMSF, Rg, H-bond, MM/PBSA binding energy) illustrated that the 8-hydroxymanzamine exhibits a static thermodynamic feature than the other two complexes. The predicted physicochemical, toxicity, pharmacokinetics, and drug-likeness profiles also revealed that the 8-hydroxymanzamine could be used as a potential lead candidate individually and/or synergistically with darunavir or lopinavir to combat SARS-CoV-2 infection after some pharmacological validation.

Prediction of COVID-19 manipulation by selective ACE inhibitory compounds of Potentilla reptant root: In silico study and ADMET profile.

In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac arrhythmias and apoptosis. Therefore, isolated components of P. reptans evaluated to identify natural anti-SARS-CoV-2 agents via molecular docking. In silico molecular docking study were carried out using the Auto Dock software on the isolated compounds of Potentilla reptans root. The protein targets of selective ACE and others obtained from Protein Data Bank (PDB). The best binding pose between amino acid residues involved in active site of the targets and compounds was discovered via molecular docking. Furthermore, ADMET properties of the compounds were evaluated. The triterpenoids of P. reptans showed more ACE inhibitory potential than catechin in both domains. They were selective on the nACE domain, especially compound 5. Also, the compound 5 & 6 had the highest binding affinity toward active site of nACE, cACE, AT1R, ACE2, and TNF-α receptors. Meanwhile, compound 3 showed more activity to inhibit TXA2. Drug likeness and ADMET analysis showed that the compounds passed the criteria of drug likeness and Lipinski rules. The current study depicted that P. reptans root showed cardioprotective effect in COVID-19 infection and manipulation of angiotensin II-induced side effects.

Proteins of SARS CoV-2, which causes COVID-19, and the Interacting proteins. (Proteins of SARS CoV-2, which causes COVID-19, and the Interacting proteins.)

This journal issue on the topic of COVID proteins features four articles: (1) A review on the biochemical activities of the nonstructural proteins (NSPs) and the spike protein and a description of a recent ribosomal profiling study that revealed 23 new SARS CoV-2 proteins (2) An in silico study of the mutational stability of SARS CoV-2 proteins (3) A docking study of milk peptides binding to various SARS CoV-2 proteins (4) A docking study of possible anti-SARS CoV-2 main protease inhibitors.

Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: an in silico study.

Novel SARS coronavirus or SARS-CoV-2 is a novel coronavirus that was identified and spread from Wuhan in 2019. On January 30th, the World Health Organization declared the coronavirus outbreak as a Global Public Health Emergency. Although Remdesivir and Molnupiravir are FDA-approved drugs for COVID-19, finding new efficient and low-cost antiviral drugs against COVID-19 for applying in more countries can still be helpful. One of the potential sources for finding new and low-cost drugs is the herbal compounds in addition to repurposing FDA-approved drugs. So, in this study, we focused on finding effective drug candidates against COVID-19 based on the computational approaches. As ACE2 serves as a critical receptor for cell entry of this virus. Inhibiting the binding site of SARS-CoV-2 on human ACE2 provides a promising therapeutic approach for developing drugs against SARS-CoV-2. Herein, we applied a bioinformatics approach to identify possible potential inhibitors of SARS-CoV-2. A library of FDA-approved compounds and five natural compounds was screened using Smina docking. Top-docking compounds are then applied in Molecular Dynamics (MD) simulation to assess the stability of ACE2-inhibitor complexes. Results indicate that Luteolin and Chrysin represent high conformation stability with ACE2 during 120 ns of Molecular Dynamics simulation. The binding free energies of Luteolin and Chrysin were calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area method (MM/PBSA) which confirmed the relative binding free energy of these drugs to ACE2 in favor of the effective binding. So, Luteolin and Chrysin could sufficiently interact with ACE2 and block the Spike binding pocket of ACE2 and can be a potential inhibitor against the binding of SARS-CoV-2 to ACE2 receptor which is an early stage of infection. Luteolin and Chrysin could be suggestive as beneficial compounds for preventing or reducing SARS-CoV-2 transmission and infection which need experimental work to prove.

SARS-CoV-2 RNA Dependent RNA polymerase (RdRp) - A drug repurposing study.

The outbreak of SARS-CoV-2 in December 2019 in China subsequently lead to a pandemic. Lack of vaccine and specific anti-viral drugs started a global health disaster. For a sustained control and protection, development of potential anti-viral drugs is one of the targeted approach. Although, designing and developing a panel of new drugs molecules are always encouraged. However, in the current emergency, drug repurposing study is one of the most effective and fast track option. The crystal structure of a SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) RNA Dependent RNA Polymerase (RdRp) has recently been deciphered through X-ray crystallography. The single-chain of core RNA Dependent RNA Polymerase relies on virus-encoded cofactors nsp7 and two units of nsp8 for its optimum function. This study explored the FDA approved database of 7922 molecules and screened against the core polymerase along with cofactors. Here we report a panel of FDA approved drugs that show substantial interactions with key amino acid residues of the active site. Interestingly, some of the identified drugs (Ornipressin, Lypressin, Examorelin, Polymyxin B1) bind strongly within the binding pockets of both forms of RdRp. Besides, we found strong candidates for the complex form as well which include Nacortocin, Cistinexine, Cisatracurium (among others). These drugs have the potential to be considered while contriving therapeutic options.

Anti-HIV-drug and phyto-flavonoid combination against SARS-CoV-2: a molecular docking-simulation base assessment.

At the health emergence, no such potent prophylactic therapy is available to control the deadly emerged Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). However, existing antiviral, anti-inflammatory, antimalarial drugs is the only option against SARS-CoV-2, but it may be harmful to patients without more clinical evidence. As an alternative solution, we proposed a newer hypothesis using the selective 10 potent anti-HIV drugs and flavonoid class of phytochemicals from previous reports to use in combination against SARS-CoV-2. Primarily, 10 anti-HIV protease inhibitor drugs and 10 phyto-flavonoids as ligands in molecular docking study against the putative target, the SARS-CoV-2-main protease (Mpro) ID: 6Y2E), as an essential enzyme in viral genome replication. According to molecular docking and drug-ability scores of each ligand, the anti-HIV drug, the darunavir (with a docking score, -10.25 kcal/mol and drug-likeness rating, 0.60) and the quercetin-3-rhamnoside (with a docking score, -10.90 kcal/mol and drug-likeness rating, 0.82) were selected for further analysis in combined effect. Perceptibly, the combined 'anti-HIV drug and phyto-flavonoid' docking complex has actively interacted with eight strong H-bonds with stability, briefly elucidated through RMRD-, RMSF- Rg-plots and MM/PBSA-binding energy calculation during 100 ns than the individual against SARS-CoV-2-Mpro. Thus, the 'anti-HIV-drug-phyto-flavonoid' combination therapy could be used against SARS-CoV-2 after some experimental validation.Communicated by Ramaswamy H. Sarma.