Repurposing drugs and identification of inhibitors of integral proteins (spike protein and main protease) of SARS-CoV-2.

Content Provider	Europe PMC
Author	Shode, F. O. Idowu, A. S. K. Uhomoibhi, O. J. Sabiu, S.
Copyright Year	2021
Abstract	AbstractThe outbreak of Coronavirus infection (COVID-19) has prompted the World Health Organisation (WHO) to declare the outbreak, a Public Health Emergency of International concern. As part of the efforts to discover lead compounds for clinical use, 53 molecules were screened using molecular docking and dynamic simulations (MDS) techniques to identify potential inhibitors of SARS-CoV-2 spike protein (COVID-19 Sgp) and main protease (COVID-19 Mpro) or both. Lopinavir (LPV), nelfinavir (NEF), hydroxychloroquine (HCQ), remdesivir (RDV) and an irreversible inhibitor of SARS-CoV (N3) were used as standard drugs for COVID-19 Mpro, while zafirlukast (ZFK) and cefoperazone (CSP)) as standard drugs for COVID-19 Sgp. After 100 ns of MDS, with reference to standard drugs (N3, −52.463 Kcal/mol, NEF, −51.618 Kcal/mol, RDV, −48.780 Kcal/mol, LPV, −46.788 Kcal/mol, DRV, −33.655 Kcal/mol and HCQ, −21.065 Kcal/mol), five molecules, HCR, GRN, C3G, EGCG, and K7G were predicted to be promising inhibitors of COVID-19 Mpro with binding energies of −53.877 kcal/mol, −50.653 Kcal/mol, −48.600 kcal/mol, −47.798 kcal/mol and −46.902 kcal/mol, respectively. These lead molecules were then docked at receptor-binding domain (RBD) of COVID-19 Sgp to examine their inhibitory effects. C3G, GRN and K7G exhibited higher binding energies of −42.310 kcal/mol, −32.210 kcal/mol, −26.922 kcal/mol than the recorded values for the reference drugs (CSP, −35.509 kcal/mol, ZFK, −24.242 kcal/mol), respectively. The results of the binding energy and structural analyses from this study revealed that C3G, GRN and K7G could serve as potential dual inhibitors of COVID-19 Sgp and COVID-19 Mpro, while HCR and EGCG would be inhibitors of COVID-19 Mpro.Communicated by Ramaswamy H. Sarma
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7898306&blobtype=pdf
Page Count	16
ISSN	07391102
Journal	Journal of Biomolecular Structure & Dynamics [J Biomol Struct Dyn]
Volume Number	40
DOI	10.1080/07391102.2021.1886993
PubMed Central reference number	PMC7898306
Issue Number	14
PubMed reference number	33590806
e-ISSN	15380254
Language	English
Publisher	Taylor & Francis
Publisher Date	2021-02-16
Access Restriction	Open
Rights License	This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections. © 2021 Informa UK Limited, trading as Taylor & Francis Group
Subject Keyword	Coronavirus infection molecular dynamic simulations spike (S) glycoprotein main protease enzyme inhibitors
Content Type	Text
Resource Type	Article
Subject	Structural Biology Medicine Molecular Biology