A molecular basis for repurposing H2-blockers to treat COVID-19.

Key Messages

Histamine H2-receptor antagonists, also known as H2-blockers, are used to treat duodenal ulcers, gastric ulcers and other conditions which cause the stomach to produce too much acid.

In this in silico study, various computer modeling methods (molecular docking, molecular dynamics simulation, MM-PBSA analysis, gene prediction analysis) tested the potential of four different H2 blockers, including famotidine, to target SARS-CoV-2 proteins.

The study concluded that famotidine and cimetidine have the potential to treat COVID-19 by targeting SARS-CoV-2 non-structural proteins which are involved in SARS-CoV-2 replication.

Journal of Biomolecular Structure and Dynamics

Publication Date: January 1, 2021
Peer Reviewed: Yes
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.1080/07391102.2021.1873191

Molecular basis for the repurposing of histamine H2-receptor antagonist to treat COVID-19

Ahmed A. Ishola, Tanuja Joshi, Suliat I. Abdulai, Habibu Tijjani, Hemlata Pundir, Subhash Chandra

Abstract

With the world threatened by a second surge in the number of Coronavirus cases, there is an urgent need for the development of effective treatment for the novel coronavirus (COVID-19). Recently, global attention has turned to preliminary reports on the promising anti-COVID-19 effect of histamine H2-receptor antagonists (H2RAs), most especially Famotidine. Therefore, this study was designed to exploit a possible molecular basis for the efficacy of H2RAs against coronavirus. Molecular docking was performed between four H2RAs, Cimetidine, Famotidine, Nizatidine, Ranitidine, and three non-structural proteins viz. NSP3, NSP7/8 complex, and NSP9. Thereafter, a 100 ns molecular dynamics simulation was carried out with the most outstanding ligands to determine the stability. Thereafter, Famotidine and Cimetidine were subjected to gene target prediction analysis using HitPickV2 and eXpression2Kinases server to determine the possible network of genes associated with their anti-COVID activities. Results obtained from molecular docking showed the superiority of Famotidine and Cimetidine compared to other H2RAs with a higher binding affinity to all selected targets. Molecular dynamic simulation and MMPBSA results revealed that Famotidine as well as Cimetidine bind to non-structural proteins more efficiently with high stability over 100 ns. Results obtained suggest that Famotidine and Cimetidine could be a viable option to treat COVID-19 with a mechanism of action that involves the inhibition of viral replication through the inhibition of non-structural proteins. Therefore, Famotidine and Cimetidine qualify for further study as a potential treatment for COVID-19.