Abstract
The present study investigated antiviral peptides (AVPs) as inhibitors of SARS-CoV-2 Orf9b protein, a novel target for disrupting the Orf9b-TOM70 complex crucial for viral infection. In silico screening via molecular docking and MD simulations identified AVP1442 and AVP1896 with high binding affinities to Orf9b (- 846.3 kcal mol(-1) and - 820 kcal mol(-1), respectively), comparable to the Orf9b-TOM70 complex (- 810.99 kcal mol(-1)). These AVPs interacted with key amino acid residues in Orf9b, including phosphorylation sites. In addition, AVPs also closely interacted with conserved regions in Orf9b. AVP1896 formed a hydrogen bond with Orf9b's threonine at position 84. AVP1442 interacted with Orf9b's leucine at position 15. Favorable Ramachandran plots and compactness during MD simulations for up to 100 ns suggest good stability of formed complexes. These non-toxic AVPs warrant further in vitro and in vivo evaluation, potentially as components of drug cocktails with small molecules or interferon-based therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-024-04032-4.