Human antimicrobial peptide Histatin 1, 3, and its autoproteolytic cleaved peptides target the monkeypox virus surface proteins: molecular modelling and docking studies

Abstract

Abstract Context Monkeypox is a viral zoonotic illness resembling smallpox. It was a national epidemic, primarily in Africa, but the recent outbreak of the monkeypox virus (MPXV) which affected numerous countries, including India. MPXV surface proteins are considered important targets, since these are involved in the virus entry into a host and cell-cell fusion(syncytial formation). Here, we suggest a novel antimicrobial peptide therapy-based method for treating MPXV infection. An in silico method was used to analyze the human antimicrobial peptides Histatin 1, 3, and its autoproteolytic cleaved products (hAMP HIS), which bind to several MPXV surface proteins. Compared to HIS 1 and 3, HIS 5 has higher solubility, estimated half-life, cell permeability, stability, and good docking score. Hence, based on the physicochemical properties of HIS 5, it may be used as a novel potential therapeutic peptide against MPXV. Current study shows hAMP HIS family may effectively target the MPXV. It would be fascinating to conduct more research on the HIS 5 peptide's effects on viral infections in both in vitro and in vivo models.Methods MPXV surface proteins and hAMP HIS localization and 3D structures was predicted by Protter, and trRosetta & c-quark respectively; 3D model refinement and validated carried out using the GalaxyRefine, Errat, Procheck, and Qmean (SwissModel). Further, molecular docking was carried out for MPXV surface proteins with hAMP HIS using HDOCK and Cluspro 2.0. Protein-peptide interactions were analyzed using PdbSum. Finally, physico-chemical property of HIS peptides was carried out using CamSol.