Elucidating host cell response pathways and repurposing therapeutics for SARS-CoV-2 and other coronaviruses

Area of Science:

• Virology
• Computational Drug Discovery
• Pharmacology

Background:

• The ongoing COVID-19 pandemic necessitates the development of effective therapeutics.
• Existing vaccines prevent severe disease, but treatment options remain crucial.
• Repurposing existing compounds offers a timely and cost-efficient approach to drug discovery.

Purpose of the Study:

• To identify and validate existing compounds for repurposing as therapeutics against SARS-CoV-2 and other coronaviruses.
• To uncover key host pathways involved in viral infection and therapeutic targeting.

Main Methods:

• Utilized a proprietary in silico engine to screen over 22,000 compounds against gene expression profiles.
• Validated 13 promising compounds through in vitro testing against SARS-CoV-2.
• Performed in-depth pathway analysis to identify molecular targets.

Main Results:

• Identified three compounds with significant in vitro potency against SARS-CoV-2.
• Bortezomib (IC50 = 1.39 μM) and Homoharringtonine (IC50 = 0.16 μM) demonstrated high efficacy.
• Tanespimycin and Homoharringtonine were also effective against common cold coronaviruses.
• Proteasome, ribosome, and heat shock pathways were identified as key targets.

Conclusions:

• The study successfully identified potent drug candidates for COVID-19 treatment through computational screening and in vitro validation.
• Targeting host pathways like the proteasome and ribosome offers a promising strategy for antiviral therapy.
• These findings provide valuable insights for the development of novel therapeutics against SARS-CoV-2 and related viruses.