Peptide inhibitors against SARS-CoV-2 2′-O-methyltransferase involved in RNA capping: A computational approach

Abstract

The COVID-19 pandemic is still evolving and is caused by SARS-CoV-2. The 2′-O-methyltransferase (nsp16) enzyme is crucial for maintaining the stability of viral RNA for effective translation of viral proteins and its life cycle. Another protein, nsp10, is important for enzymatic activity of nsp16. Any disturbance in the interaction between nsp16 and nsp10 may affect viral replication fidelity. Here, five peptide inhibitors, derived from nsp16, were designed and assessed for their effectiveness in binding to nsp10 using molecular dynamics simulation. The inhibitors were derived from the nsp10/nsp16 binding interface. Post-simulation analysis showed that inhibitors 2 and 5 were stable and bind to the nsp16 interacting region of nsp10 which could potentially prevent the interaction between the two proteins. The proposed peptides are useful starting points for the development of therapeutics to manage the spread of COVID-19.

Keywords

• SARS-CoV-2
• Nsp16
• Nsp10
• Peptide inhibitors
• Therapeutics
• Molecular dynamics simulation