A Study of Drug Repurposing to Identify SARS-CoV-2 Main Protease (3CLpro) Inhibitors

Area of Science:

• Virology
• Pharmacology
• Computational Biology

Background:

• The COVID-19 pandemic caused by SARS-CoV-2 necessitates effective treatments.
• Drug repurposing offers a rapid strategy for identifying existing therapies for new uses.
• Existing vaccines do not eliminate the need for accessible therapeutic options.

Purpose of the Study:

• To identify existing drugs with inhibitory activity against SARS-CoV-2.
• To evaluate the antiviral efficacy and safety of repurposed drug candidates.
• To discover novel treatments for COVID-19 through computational and in vitro screening.

Main Methods:

• Utilized Artificial Intelligence (AI) technology (SOM AI PRO) and in silico docking to screen a chemical library.
• Selected thirty Phase II-and-up compounds with established safety profiles.
• Performed in vitro testing for inhibitory activity against SARS-CoV-2 main protease (3CLpro) and assessed cell protection in infected VeroE6 cells.

Main Results:

• Three compounds (cynarine, eravacycline, prexasertib) demonstrated significant inhibition of SARS-CoV-2 3CLpro.
• Eravacycline exhibited potential antiviral activity in cell-based assays.
• Eravacycline showed no significant cytotoxicity, indicating a favorable safety profile.

Conclusions:

• Eravacycline is a promising candidate for further development as a COVID-19 therapeutic.
• Drug repurposing combined with AI and in silico methods is effective for identifying potential antivirals.
• Further pre-clinical studies are planned to validate eravacycline's efficacy and safety.