Rilpivirine inhibits SARS-CoV-2 protein targets: A potential multi-target drug.

Fuad Ameen, Estari Mamidala, Rakesh Davella, Shravan Vallala,

10.1016/j.jiph.2021.07.012

Research curated

Abstract

Background COVID-19 disease caused by SARS-CoV-2 is lacking efficient medication although certain medications are used to relief its symptoms. Objectives We tested an FDA-approved antiviral medication namely rilpivirine to find a drug against SARS-CoV-2. Methods The inhibition of rilpivirine against multiple SARS-CoV-2 therapeutic targets was studied using in silico method. The binding attraction of the protein-ligand complexes were calculated using molecular docking analysis. Results Docking rilpivirine with main protease (Mpro), papin like protease (PLpro), sprike protein (Spro), human angiotensin converting enzyme-2 (ACE2), and RNA dependent-RNA polymerase (RdRp) yielded binding energies of −8.07, −8.40, −7.55, −9.11, and −8.69 kcal/mol, respectively. The electrostatic interaction is the key force in stabilizing the RdRp-rilpivirine complex, while van der Waals interaction dominates in the ACE2 rilpivirine case. Our findings suggest that rilpivirine can inhibit SARS-CoV-2 replication by targeting not only ACE2, but also RdRp and other targets, and therefore, it can be used to invoke altered mechanisms at the pre-entry and post-entry phases. Conclusion As a result of our in silico molecular docking study, we suggest that rilpivirine is a compound that could act as a powerful inhibitor against SARS-CoV-2 targets. Although in vitro and in vivo experiments are needed to verify this prediction we believe that this antiviral drug may be used in preclinical trials to fight against SARS coronavirus.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Rilpivirine
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Angiotensin-converting enzyme 2	ACE-related carboxypeptidase, ACE2	ACE2
3C-like protease	3CLpro, Mpro, SARS coronavirus main peptidase, 3CLpro-SARS-CoV-2	rep, ORF1a-1b
Papain-like proteinases 1/2	Non-structural protein 3, papain like viral protease, nsp3, PL1-PRO/PL2-PRO, PLP1/PLP2, p195, Plpro	rep, ORF1a-1b

Related interactions

Target	Drug	Type	Result
Spike glycoprotein	Rilpivirine	Computational	positive
Angiotensin-converting enzyme 2	Rilpivirine	Computational	positive
3C-like protease	Rilpivirine	Computational	positive
Papain-like proteinases 1/2	Rilpivirine	Computational	positive