Issue 17, 2021

Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study

Abstract

The global breakout of COVID-19 and raised death toll has prompted scientists to develop novel drugs capable of inhibiting SARS-CoV-2. Conducting studies on repurposing some FDA-approved glucocorticoids can be a promising prospective for finding a treatment for COVID-19. In addition, the use of anti-inflammatory drugs, such as glucocorticoids, is a pivotal step in the treatment of critical cases of COVID-19, as they can provoke an inflammatory cytokine storm, damaging lungs. In this study, 22 FDA-approved glucocorticoids were identified through in silico (molecular docking) studies as the potential inhibitors of COVID-19's main protease. From tested compounds, ciclesonide 11, dexamethasone 2, betamethasone 1, hydrocortisone 4, fludrocortisone 3, and triamcinolone 8 are suggested as the most potent glucocorticoids active against COVID-19's main protease. Moreover, molecular dynamics simulations followed by the calculations of the binding free energy using MM-GBSA were carried out for the aforementioned promising candidate-screened glucocorticoids. In addition, quantum chemical calculations revealed two electron-rich sites on ciclesonide where binding interactions with the main protease and cleavage of the prodrug to the active metabolite take place. Our results have ramifications for conducting preclinical and clinical studies on promising glucocorticoids to hasten the development of effective therapeutics against COVID-19. Another advantage is that some glucocorticoids can be prioritized over others for the treatment of inflammation accompanying COVID-19.

Graphical abstract: Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study

Supplementary files

Article information

Article type
Paper
Submitted
19 Dec 2020
Accepted
17 Feb 2021
First published
09 Mar 2021
This article is Open Access
Creative Commons BY license

RSC Adv., 2021,11, 10027-10042

Revisiting activity of some glucocorticoids as a potential inhibitor of SARS-CoV-2 main protease: theoretical study

A. A. Elmaaty, R. Alnajjar, M. I. A. Hamed, M. Khattab, M. M. Khalifa and A. A. Al-Karmalawy, RSC Adv., 2021, 11, 10027 DOI: 10.1039/D0RA10674G

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