Background: Monkeypox, a viral zoonotic disease akin to smallpox, has posed significant public health challenges, particularly in Africa. Recent outbreaks, including those in India, underscore the global threat it poses. Objective: In this study, we explore a novel approach to combat monkeypox virus (MPXV) infection by targeting its surface proteins, crucial for viral entry and fusion. Methods: Employing advanced computational techniques, we predict and refine the 3D structures of MPXV surface proteins and human antimicrobial peptides (hAMPs), specifically Histatin 1, 3, and their cleaved product, Histatin 5 (HIS 5). 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, the physicochemical properties of HIS peptides were determined using CamSol. Results: Our findings suggest HIS 5 as a potential therapeutic peptide against MPXV, warranting further investigation through in vitro and in vivo studies. result: Compared to HIS 1 and 3, HIS 5 has higher solubility, an estimated half-life, cell permeability, stability, and a good docking score. Hence, based on the physicochemical properties of HIS 5, it may be used as a novel potential therapeutic peptide against MPXV. Conclusion: This study sheds light on the efficacy of the HIS family in targeting MPXV and advocates for continued exploration of HIS 5's antiviral effects.
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