Repurposing of human defensins as a promising antiviral therapeutics against SARS-CoV-2

Human defensins are also known to have promising antiviral activities against both enveloped and non-enveloped viruses. The world has already faced panic during the COVID-19 pandemic and alarms us to get ready to fight the emergence of new highly mutated variants. Overall, there is an urgent need for promising antivirals to combat the SARS-CoV-2 and related viral pathogens. Considering the antiviral potential of human defensins, we have analyzed known human defensins against SARS-CoV-2 Spike protein and its human cell surface receptor angiotensin-converting enzyme 2 (ACE2) for binding affinities. Our molecular docking analysis revealed that defensins could block the SARS-CoV-2 entry into the cell by interacting and blocking of viral S protein, cell surface receptor ACE2, and the complex of both. Further, validation by employing molecular dynamics (MD) simulations showed HNP2 and HD5 as potential candidates to restrict SARS-CoV-2 entry among all analyzed human defensins. Interestingly, gene expression analysis of human defensins using available datasets is in agreement with the MD simulation results. In conclusion, results suggest HNP2 and HD5 as potential candidates that could be further investigated for the development of peptide-based vaccines and other therapeutic applications to combat SARS-CoV-2 and other related viral pathogens. • This study revealed HNP2 and HD5 as potential candidates to fight against SARS-CoV-2. • Binding affinities of HNP2 and HD5 with SARS-CoV-2 spike protein and complex are validated with molecular dynamics and simulation studies. • Publically available gene expression data sets of defensins were analyzed and found in agreement with our interaction studies. • This study suggested human defensins could be developed as antiviral therapeutics.