Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2

Ahmad F. Eweas, Amr A. Alhossary, Ahmed S. Abdel-Moneim4

10.3389/fmicb.2020.592908

Research curated

Abstract

SARS-CoV-2 is a newly emerged coronavirus that causes a respiratory disease with variable severity and fatal consequences. It was first reported in Wuhan and subsequently caused a global pandemic. The viral spike protein binds with the ACE-2 cell surface receptor for entry, while TMPRSS2 triggers its membrane fusion. In addition, RNA dependent RNA polymerase (RdRp), 3′–5′ exoribonuclease (nsp14), viral proteases, N, and M proteins are important in different stages of viral replication. Accordingly, they are attractive targets for different antiviral therapeutic agents. Although many antiviral agents have been used in different clinical trials and included in different treatment protocols, the mode of action against SARS-CoV-2 is still not fully understood. Different potential repurposed drugs, including, chloroquine, hydroxychloroquine, ivermectin, remdesivir, and favipiravir, were screened in the present study. Molecular docking of these drugs with different SARS-CoV-2 target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral proteases, and nsp14, was performed. Moreover, the binding affinities of the human ACE-2 receptor and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to be the most promising drugs. Our results suggest that both these drugs utilize different mechanisms at the entry and post-entry stages and could be considered potential inhibitors of SARS-CoV-2 replication.

Source: PMC

Related molecules

Name	Synonyms	Genes
Ivermectin	IVERMECTIN, Ivermectin B1a, Dihydroavermectin B1a, 70288-86-7, 22-23-Dihydroavermectin B1a
Transmembrane serine 2	TMPRSS2, Serine protease 10	TMPRSS2, PRSS10
Exoribonuclease	ExoN, Non-structural protein14, Nonstructural protein14, nsp14, 5‘-to-3‘ exonuclease	rep, ORF1a-1b
Remdesivir
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	Ivermectin	Computational	positive
Angiotensin-converting enzyme 2	Ivermectin	Computational	positive
Transmembrane serine 2	Ivermectin	Computational	positive
3C-like protease	Ivermectin	Computational	positive
Papain-like proteinases 1/2	Ivermectin	Computational	positive
Exoribonuclease	Ivermectin	Computational	positive
Papain-like proteinases 1/2	Remdesivir	Computational	positive
3C-like protease	Remdesivir	Computational	positive
RNA dependent RNA polymerase	Remdesivir	Computational	positive
Exoribonuclease	Remdesivir	Computational	positive