A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing

Area of Science:

• Virology
• Genomics
• Drug Discovery

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, causing a global pandemic with significant respiratory illness.
• The virus's high mutation rate complicates the development of effective therapeutics due to rapid evolution and genome variability.

Purpose of the Study:

• To identify common SARS-CoV-2 haplotypes and analyze conserved genes and population-level variants.
• To target conserved viral proteins for potential therapeutic interventions.
• To investigate mutation frequencies across the SARS-CoV-2 genome.

Main Methods:

• Haplotype network analysis to identify common viral strains.
• Analysis of conserved genes and population variants.
• Molecular dynamics simulations targeting conserved proteins like NSP10, Nucleoprotein, Plpro (NSP3), and 3CLpro (NSP5).

Main Results:

• Identified common SARS-CoV-2 haplotypes and key conserved genes.
• Non-Structural Protein 10 (NSP10), Nucleoprotein, Papain-like protease (Plpro or NSP3), and 3-Chymotrypsin like protease (3CLpro or NSP5) were identified as highly conserved drug targets.
• Identified mutation frequencies across the viral genome.

Conclusions:

• The study provides a comprehensive targeting strategy for conserved SARS-CoV-2 genes.
• Potential drugs including Darifenacin, Nebivolol, Bictegravir, Alvimopan, and Irbesartan were identified for further pre-clinical and clinical evaluation.
• Understanding viral genome variability and conserved targets is crucial for developing robust therapeutics against SARS-CoV-2.