Structure-based drug designing and immunoinformatics approach for SARS-CoV-2

Area of Science:

• Virology
• Drug Discovery
• Immunoinformatics

Background:

• The novel SARS-CoV-2 virus causes respiratory illness and multi-organ failure, spreading globally due to human transmission and healthcare system limitations.
• Pharmaceutical repurposing offers a cost-effective and time-efficient strategy for developing new therapeutics compared to de novo discovery.

Purpose of the Study:

• To virtually screen antiviral compounds against critical SARS-CoV-2 targets, including the spike glycoprotein (S), main protease (Mpro), and the RBD-ACE2 complex.
• To evaluate the binding affinity and conformational effects of promising drug candidates.
• To explore the use of immunoinformatics for identifying potential vaccine epitopes.

Main Methods:

• Virtual screening of antiviral compounds against SARS-CoV-2 S protein, Mpro, and RBD-ACE2 complex.
• Assessment of binding affinity and molecular interactions of identified compounds.
• Computational identification of T cell and B cell epitopes using immunoinformatics tools.

Main Results:

• PC786, an antiviral polymerase inhibitor, demonstrated significant binding affinity to all screened SARS-CoV-2 targets.
• Drug binding of PC786 induced conformational changes in the S protein RBD-ACE2 complex.
• Immunoinformatics analysis identified potential epitopes for vaccine development.

Conclusions:

• PC786 is a potential repurposed drug candidate for treating SARS-CoV-2 infections.
• Computational methods can effectively guide the discovery of antiviral therapeutics and vaccine candidates.
• Further experimental validation is warranted to confirm the efficacy and safety of PC786 and identified epitopes.