Repurposing fusion inhibitor peptide against <scp>SARS‐CoV</scp> ‐2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for viral pathogen due their efficacy, safety, and specificity. In study, seventeen antiviral peptides which known inhibit SARS-CoV-1 collected computationally screened heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out 17 peptides, Fp13 Fp14 showed better binding affinity toward HR1 compared control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore time-dependent interactions with HR1, dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural energy parameters Fp13-HR1 Fp14-HR1 complexes demonstrated lower fluctuations EK1-HR1 complex. Furthermore, principal component analysis free landscape study revealed that these two (Fp13 Fp14) strongly bind higher than EK1. Tyr917, Asn919, Gln926, lys933, Gln949 residues found be crucial interaction. Notably, Fp13, reasonably hydrogen bond contribution Taken together, may highly specific can potentially prevent formation core could further developed as therapeutics treatment or prophylaxis infection.