Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches

Hourieh Kalhor, Solmaz Sadeghi, Hoda Abolhasani, Reyhaneh Kalhor, Hamzeh Rahimi

10.1080/07391102.2020.1824816

Research curated

Abstract

Most recently, the new coronavirus (SARS-CoV-2) has been recognized as a pandemic by the World Health Organization (WHO) while this virus shares substantial similarity with SARS-CoV. So far, no definitive vaccine or drug has been developed to cure Covid-19 disease, since many important aspects about Covid-19 such as pathogenesis and proliferation pathways are still unclear. It was proven that human ACE2 is the main receptor for the entry of Covid-19 into lower respiratory tract epithelial cells through interaction with SARS-CoV-2 S protein. Based on this observation, it is expected that the virus infection can be inhibited if protein-protein interaction is prevented. In this study, using structure-based virtual screening of FDA databases, several lead drugs were discovered based on the ACE2-binding pocket of SARS-CoV-2 S protein. Then, binding affinity, binding modes, critical interactions, and pharmaceutical properties of the lead drugs were evaluated. Among the previously approved drugs, Diammonium Glycyrrhizinate, Digitoxin, Ivermectin, Rapamycin, Rifaximin, and Amphotericin B represented the most desirable features, and can be possible candidates for Covid-19 therapies. Furthermore, molecular dynamics (MD) simulation was accomplished for three S protein/drug complexes with the highest binding affinity and best conformation and binding free energies were also computed with the Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Results demonstrated the stable binding of these compounds to the S protein; however, in order to confirm the curative effect of these drugs, clinical trials must be done.

Source: PubMed

Related molecules

Name	Synonyms	Genes
Diammonium Glycyrrhizinate
Rifaximin
Rapamycin
Amphotericin B
Spike glycoprotein	Spike protein, S glycoprotein, S-Protein, S1, S2, S3, Peplomer protein, E2	S, ORF2
Digitoxin
Ivermectin	IVERMECTIN, Ivermectin B1a, Dihydroavermectin B1a, 70288-86-7, 22-23-Dihydroavermectin B1a

Related interactions

Target	Drug	Type	Result
Spike glycoprotein	Diammonium Glycyrrhizinate	Computational	positive
Spike glycoprotein	Rifaximin	Computational	positive
Spike glycoprotein	Rapamycin	Computational	positive
Spike glycoprotein	Digitoxin	Computational	positive
Spike glycoprotein	Ivermectin	Computational	positive