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Molecular docking and simulation studies on SARS-CoV-2 Mpro reveals Mitoxantrone, Leucovorin, Birinapant, and Dynasore as potent drugs against COVID-19.
Lokhande, Kiran Bharat; Doiphode, Sayali; Vyas, Renu; Swamy, K Venkateswara.
  • Lokhande KB; Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Patil Vidyapeeth, Pune, India.
  • Doiphode S; Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Patil Vidyapeeth, Pune, India.
  • Vyas R; Bioinformatics Research Group, MIT School of Bioengineering Science and Research, MIT- ADT University, Pune, India.
  • Swamy KV; Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Patil Vidyapeeth, Pune, India.
J Biomol Struct Dyn ; 39(18): 7294-7305, 2021 11.
Article in English | MEDLINE | ID: covidwho-724957
ABSTRACT
The outbreak of novel coronavirus (COVID-19), which began from Wuhan City, Hubei, China, and declared as a Public Health Emergency of International Concern by World Health Organization (WHO) on 30th January 2020. The present study describes how the available drug candidates can be used as a potential SARS-CoV-2 Mpro inhibitor by molecular docking and molecular dynamic simulation studies. Drug repurposing strategy is applied by using the library of antiviral and FDA approved drugs retrieved from the Selleckchem Inc. (Houston, TX, http//www.selleckchem.com) and DrugBank database respectively. Computational methods like molecular docking and molecular dynamics simulation were used. The molecular docking calculations were performed using LeadIT FlexX software. The molecular dynamics simulations of 100 ns were performed to study conformational stability for all complex systems. Mitoxantrone and Leucovorin from FDA approved drug library and Birinapant and Dynasore from anti-viral drug libraries interact with SARS-CoV-2 Mpro at higher efficiency as a result of the improved steric and hydrophobic environment in the binding cavity to make stable complex. Also, the molecular dynamics simulations of 100 ns revealed the mean RMSD value of 2.25 Å for all the complex systems. This shows that lead compounds bound tightly within the Mpro cavity and thus having conformational stability. Glutamic acid (Glu166) of Mpro is a key residue to hold and form a stable complex of reported lead compounds by forming hydrogen bonds and salt bridge. Our findings suggest that Mitoxantrone, Leucovorin, Birinapant, and Dynasore represents potential inhibitors of SARS-CoV-2 Mpro.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pharmaceutical Preparations / COVID-19 Limits: Humans Language: English Journal: J Biomol Struct Dyn Year: 2021 Document Type: Article Affiliation country: 07391102.2020.1805019

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pharmaceutical Preparations / COVID-19 Limits: Humans Language: English Journal: J Biomol Struct Dyn Year: 2021 Document Type: Article Affiliation country: 07391102.2020.1805019