Drug repurposing using computational methods to identify therapeutic options for COVID-19

Area of Science:

• Virology
• Drug Discovery
• Computational Chemistry

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 necessitates urgent therapeutic strategies.
• Existing treatments for COVID-19 are limited, highlighting the need for novel approaches.
• Drug repurposing offers an efficient pathway to identify existing medications for new therapeutic uses.

Purpose of the Study:

• To identify potential therapeutic agents for COVID-19 through drug repurposing.
• To screen FDA-approved drugs against critical SARS-CoV-2 target proteins.
• To evaluate drug candidates using virtual screening and binding energy analysis.

Main Methods:

• Homology modeling was used to construct five key SARS-CoV-2 proteins: 3CLpro, PLpro, cleavage site, HR1, and RBD.
• Virtual screening was performed on 2471 FDA-approved drugs against the cleavage site and RBD.
• Further screening of 18 promising antiviral drug candidates was conducted against ACE2, 3CLpro, PLpro, HR1, and TMPRSS2.

Main Results:

• 128 FDA-approved drugs exhibited favorable binding energies with the cleavage site and RBD of SARS-CoV-2.
• Glecaprevir, paritaprevir, simeprevir, ledipasvir, glycyrrhizic acid, TMC-310911, and hesperidin demonstrated high binding affinity across all tested viral targets.
• These compounds showed significant potential for inhibiting viral replication.

Conclusions:

• Several FDA-approved drugs, including glecaprevir and hesperidin, show promise as COVID-19 therapeutics.
• These identified drugs warrant further investigation for their clinical efficacy against SARS-CoV-2 infections.
• The study supports drug repurposing as a viable strategy for rapid development of COVID-19 treatments.