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1.
Virusdisease ; : 1-7, 2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1336149

ABSTRACT

A novel coronavirus disease (COVID-19), caused by SARS-CoV-2, has spread over more than 100 countries all over the world. The World Health Organization has recognized Coronavirus as a pandemic and finding an effective drug for this infectious disease is of high importance. In this study, we have explored the potent inhibitors of COVID-19 main protease from Tinospora cordifolia an Ayurvedic herb locally called as Amrita meaning 'immortality' and two other Ayurveda plants namely Cinnamomum zeylanicum and Myristica fragrans. Saponarin, a phytochemical present in Tinospora cordifolia showed a very promising result with the binding affinity of - 8.75 kcal/mol. Remdesivir and Favipiravir, the experimental drugs that are known to show inhibitory activity towards COVID-19 are used as a control. The Docking results were verified by the means of molecular dynamic analysis. This study suggests that Saponarin can be a potential inhibitor for the main protease of the COVID-19.

2.
J Mol Recognit ; 34(10): e2918, 2021 10.
Article in English | MEDLINE | ID: covidwho-1270481

ABSTRACT

The novel coronavirus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) or COVID-19 has caused a worldwide pandemic. The fatal virus has affected the health of human beings as well as the socio-economic situation all over the world. To date, no concrete medicinal solution has been proposed to combat the viral infection, calling for an urgent, strategic, and cost-effective drug development approach that may be achievable by applying targeted computational and virtual screening protocols. Immunity is the body's natural defense against disease-causing pathogens, which can be boosted by consuming plant-based or natural food products. Active constituents derived from natural sources also scavenge the free radicals and have anti-inflammatory activities. Herbs and spices have been used for various medicinal purposes. In this study, 2,96 365 natural and synthetic derivatives (ligands) belonging to 102 classes of compounds were obtained from PubChem and assessed on Lipinski's parameters for their potential bioavailability. Out of all the derivatives, 3254 obeyed Lipinski's rule and were virtually screened. The 115 top derivatives were docked against SARS-CoV-2, SARS-CoV, MERS-CoV, and HCoV-HKV1 main proteases (Mpro s) as receptors using AutoDock Vina, AutoDock, and iGEMDOCK 2.1. The lowest binding energy was exhibited by ligands 2 and 6 against all the four Mpro s. The molecular dynamic simulation was also performed with ligand 6 using the GROMACS package. Good bioactivity scores, absorption, distribution, metabolism, excretion, and toxicity profile and drug-like pharmacokinetic parameters were also obtained. Hydroxychloroquine was used as the control drug.


Subject(s)
Antiviral Agents/pharmacology , Drug Evaluation, Preclinical/methods , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Biological Availability , Blood-Brain Barrier/drug effects , Computer Simulation , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Humans , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation
3.
Sci Rep ; 11(1): 4516, 2021 02 25.
Article in English | MEDLINE | ID: covidwho-1104540

ABSTRACT

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about thirty million confirmed cases worldwide as of September 2020. Being an airborne infection, it can be catastrophic to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can act as an effective vaccine epitope candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to be studied to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as an epitope candidate. The candidacy was further analyzed using sequence conservation studies and molecular dynamics simulation. The identified epitopes can be subjected to further studies for the development of the SARS-CoV-2 vaccine.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , HLA Antigens/immunology , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , India/epidemiology , Molecular Docking Simulation , Viral Proteins/immunology
4.
SN Compr Clin Med ; : 1-10, 2020 Sep 25.
Article in English | MEDLINE | ID: covidwho-807594

ABSTRACT

The pandemic of coronavirus infection 2019 (COVID-19) due to the serious respiratory condition created by the coronavirus 2 (SARS-CoV-2) presents a challenge to recognize effective strategies for management and treatment. In general, COVID-19 is an acute disease that can also be fatal, with an ongoing 10.2% case morbidity rate. Extreme illness may bring about death because of enormous alveolar damage and hemorrhage along with progressive respiratory failure. The rapidly expanding information with respect to SARS-CoV-2 research suggests a substantial number of potential drug targets. The most encouraging treatment to date is suggested to be with the help of remdesivir, hydroxychloroquine, and many such repurposed drugs. Remdesivir has a strong in vitro activity for SARS-CoV-2, yet it is not the drug of choice as affirmed by the US Food and Drug Administration and presently is being tried in progressing randomized preliminaries. The COVID-19 pandemic has been the worst worldwide general health emergency of this age and, possibly, since the pandemic influenza outbreak of 1918. The speed and volume of clinical preliminaries propelled to examine potential treatments for COVID-19 feature both the need and capacity to create abundant evidence even in the center of a pandemic. No treatments have been demonstrated as accurate and dependable to date. This review presents a concise precise of the targets and broad treatment strategies for the benefit of researchers.

5.
J Biomol Struct Dyn ; 39(18): 7306-7321, 2021 11.
Article in English | MEDLINE | ID: covidwho-726980

ABSTRACT

Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), (Coronavirus Disease 2019). Currently, there is no specific drug for the therapy of COVID-19. So, there is a need to develop or find out the new drug from the existing to cure the COVID-19. Identification of a potent inhibitor of Methyltransferase, Endoribonuclease, Phosphatase and Main Protease enzymes of SARS CoV-2 by coumarin derivatives using insilico approach. The in silico studies were performed on maestro 12.0 software (Schrodinger LLC 2019, USA). Two thousand seven hundred fifty-five biologically active coumarin derivative was docked with above receptor proteins of SARS CoV-2. The molecular dynamic simulation of the top one ligand of respected proteins was performed. Top five ligands of each protein were taken for study. Coumarin derivatives actively interact with taken receptors and showed good docking results for Methyltransferase, Endoribonuclease, Phosphatase and Main Protease and top five compounds of each have docking score from -9.00 to -7.97, -8.42 to -6.80, -8.63 to -7.48 and -7.30 to -6.01 kcal/mol, respectively. The docked compounds were showed RMSD and binding stability of simulated ligands are show the potency of ligands against the SARS CoV-2. Our study provides information on drugs that may be a potent inhibitor of COVID-19 infection. Drug repurposing of the available drugs would be great help in the treatment of COVID-19 infection. The combination therapy of the finding may improve inhibitory activity. Communicated by Ramaswamy H. SarmaHighlightsCoronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).In silico virtual screening, docking, ADME, MM-GBSA and MD simulation analysis of coumarin derivatives against Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and Main Protease enzyme of SARS CoV-2.All the analysis was performed on Maestro 12.0 Schrodinger software against respective receptors.Top five compounds of coumarin derivatives s docked at the active site of Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and protease and top five compounds of each have docking score from -9.00 to -7.97, -8.42 to -6.80, -8.63 to -7.48 and -7.30 to -6.01 kcal/mol, respectively, of SARS CoV-2.These compounds were used to analysis of binding free energy by using the Prime MM-GBSA module.All the compounds showed drug-likeness properties.MD simulation of Proteins and ligands showed binding stability and good RMSD, radius of gyration of protein, coulomb-SR and LJ-SR energy.


Subject(s)
COVID-19 , SARS-CoV-2 , Coumarins , Endoribonucleases , Humans , Methyltransferases , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Phosphoric Monoester Hydrolases , Protease Inhibitors/pharmacology
6.
J Recept Signal Transduct Res ; 40(6): 605-612, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-457256

ABSTRACT

Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from -6.8 to -5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research.HighlightsNSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs.NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions.Compounds show good DG binging free energy with protein complexes.Ligands were found to follow the Lipinski rule of five.


Subject(s)
Antiviral Agents/chemistry , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Viral Nonstructural Proteins/chemistry , Viral Regulatory and Accessory Proteins/chemistry , Acyclovir/analogs & derivatives , Acyclovir/chemistry , Acyclovir/therapeutic use , Ancitabine/chemistry , Ancitabine/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/virology , Drug Evaluation, Preclinical , Guanine , Humans , Meropenem/chemistry , Meropenem/therapeutic use , Methyltransferases , Models, Molecular , Molecular Docking Simulation , Pandemics , Pneumonia, Viral/virology , Protein Conformation/drug effects , Ribitol/chemistry , Ribitol/therapeutic use , SARS-CoV-2 , Trifluridine/chemistry , Trifluridine/therapeutic use , User-Computer Interface , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/ultrastructure , Viral Regulatory and Accessory Proteins/antagonists & inhibitors , Viral Regulatory and Accessory Proteins/ultrastructure
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