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Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation.

ABSTRACT: Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally. Communicated by Ramaswamy H. Sarma.

SUBMITTER: Kumar D

PROVIDER: S-EPMC7332863 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation.

Kumar Durgesh D Kumari Kamlesh K Vishvakarma Vijay Kumar VK Jayaraj Abhilash A Kumar Dhiraj D Ramappa Venkatesh Kumar VK Patel Rajan R Kumar Vinod V Dass Sujata K SK Chandra Ramesh R Singh Prashant P

Journal of biomolecular structure & dynamics 20200622 13

Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to ...[more]

PMID: 32567995

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Project description:BackgroundThe rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding.MethodsFor the study, we have targeted the SARS-CoV-2 Mpro for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 Mpro active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries.ResultsThe phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir-Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 Mpro protein.ConclusionsIn the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir-Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.

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Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation.

Publications

Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation.

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