In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage

E Sila Ozdemir; Hillary H Le; Adem Yildirim; Srivathsan V Ranganathan

doi:10.3390/v14061129

In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage

Viruses. 2022 May 24;14(6):1129. doi: 10.3390/v14061129.

Authors

E Sila Ozdemir¹, Hillary H Le¹, Adem Yildirim^{1

2}, Srivathsan V Ranganathan^{1

2}

Affiliations

¹ Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA.
² Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97201, USA.

Abstract

The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting spike (S) protein cleavage by several proteases. We developed a computational pipeline to repurpose FDA-approved drugs to inhibit protease activity and thus prevent S protein cleavage. We tested some of our drug candidates and demonstrated a decrease in protease activity. We believe our pipeline will be beneficial in identifying a drug regimen for COVID-19 patients.

Keywords: SARS-CoV-2; drug repurposing; in silico screening; molecular modeling; proteases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
COVID-19*
Drug Evaluation, Preclinical
Drug Repositioning
Humans
Molecular Docking Simulation
Peptide Hydrolases
SARS-CoV-2*
Spike Glycoprotein, Coronavirus / metabolism
Virus Internalization

Substances

Antiviral Agents
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Peptide Hydrolases

Grants and funding

This work was supported by the Cancer Early Detection Advanced Research Center at Oregon Health & Science University (Exploratory7490320 and Exploratory 2020-1300).