Repurposing low-molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2

26Citations
Citations of this article
73Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The coronavirus disease pandemic caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected the global healthcare system. As low-molecular-weight drugs have high potential to completely match interactions with essential SARS-CoV-2 targets, we propose a strategy to identify such drugs using the fragment-based approach. Herein, using ligand- and protein-observed fragment screening approaches, we identified niacin and hit 1 binding to the catalytic pocket of the main protease (Mpro) of SARS-CoV-2, thereby modestly inhibiting the enzymatic activity of Mpro. We further searched for low-molecular-weight drugs containing niacin or hit 1 pharmacophores with enhanced inhibiting activity, e.g., carmofur, bendamustine, triclabendazole, emedastine, and omeprazole, in which omeprazole is the only one binding to the C-terminal domain of SARS-CoV-2 Mpro. Our study demonstrates that the fragment-based approach is a feasible strategy for identifying low-molecular-weight drugs against the SARS-CoV-2 and other potential targets lacking specific drugs.

Cite

CITATION STYLE

APA

Gao, J., Zhang, L., Liu, X., Li, F., Ma, R., Zhu, Z., … Ruan, K. (2020). Repurposing low-molecular-weight drugs against the main protease of severe acute respiratory syndrome coronavirus 2. Journal of Physical Chemistry Letters, 11(17), 7267–7272. https://doi.org/10.1021/ACS.JPCLETT.0C01894

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free