Molecular docking and simulation studies on SARS-CoV-2 Mpro reveals Mitoxantrone, Leucovorin, Birinapant, and Dynasore as potent drugs against COVID-19.
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.
Keywords
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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