Abstract:
The ongoing COVID-19 pandemic caused by the SARS-CoV-2 virus has created an urgent need for effective therapeutic interventions. Pradimicin A, a natural product isolated from Streptomyces, has shown promising antiviral activity against various enveloped viruses, including SARS-CoV-2, by targeting the viral N-glycan. However, the molecular details of how pradimicin A interacts with the N-glycan and inhibits viral entry remain unclear. We performed molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) experiments to investigate the molecular basis of pradimicin A binding to the SARS-CoV-2 N-glycan. Our results suggest that pradimicin A forms stable complexes with the N-glycan through hydrogen bonding, electrostatic interactions, and hydrophobic contacts. In particular, the 2,6-diaminoglucose and 3,4,6-trihydroxyphenyl moieties of pradimicin A play crucial roles in binding to the N-glycan. Additionally, SPR experiments confirmed the direct interaction between pradimicin A and the N-glycan. Overall, our study provides insights into the molecular mechanisms underlying pradimicin A's antiviral activity and highlights its potential as a lead compound for the development of novel SARS-CoV-2 entry inhibitors.
