In Silico Analysis of Honey Bee Peptides as Potential Inhibitors of Capripoxvirus DNA-Directed RNA Polymerase

SIMPLE SUMMARY: The viruses of the Capripoxvirus genus (i.e., sheeppox, goatpox, and lumpy skin disease viruses) pose significant financial threats to the livestock industry, causing decreased animal product output. The current study was aimed to determine the evolutionary relationships of Capripoxvirus with other Poxviridae family members through phylogenetic analysis and assess the antiviral potential of honey bee peptides against SPPV, GTPV, and LSDV. Protein–protein docking experiments were conducted, focusing on the interactions between honey bee peptides and the DNA-directed RNA polymerase of these viruses. Among the five peptides tested, mellitin and secapin-1 displayed the most favorable results, with the lowest binding scores and stable complexes. Molecular dynamics simulation further confirmed the strong connection between the protein DNA-dependent RNA polymerase and the melittin peptide, suggesting stable binding. These findings demonstrate the potential of bee peptides, particularly mellitin and secapin-1, as effective antimicrobial agents against SPPV, GTPV, and LSDV, offering a promising avenue for future research and development of antiviral therapies. ABSTRACT: The genus Capripoxvirus belongs to the Poxviridae family. The sheeppox, goatpox, and lumpy skin disease viruses are three species of this genus with 96% identity in their genomes. These are financially devastating viral infections among cattle, which cause a reduction in animal products and lead to a loss in livestock industries. In the current study, the phylogenetic analysis was carried out to reveal the evolutionary relationships of Capripoxvirus species (i.e., sheeppox virus (SPPV), goatpox virus (GTPV), and lumpy skin disease virus (LSDV)) with other viruses from the Poxviridae family with >96% query coverage to find the similarity index among all members. The three viruses (i.e., SPPV, GTPV, and LSDV) joined the clade of Capripoxvirus of the Poxviridae family in the phylogenetic tree and exhibited close evolutionary relationships. The multiple sequence alignment using ClustalOmega revealed significant variations in the protein sequences of the DNA-dependent RNA polymerase of SPPV, GTPV, and LSDV. The three-dimensional structures of five selected bee peptides and DNA-directed RNA polymerase of SPPV, GTPV, and LSDV were predicted using trRosetta and I-TASSER and used for molecular docking and simulation studies. The protein–protein docking was carried out using HADDOCK server to explore the antiviral activity of peptides as honey bee proteins against SPPV, GTPV, and LSDV. In total, five peptides were docked to DNA-directed RNA polymerase of these viruses. The peptides mellitin and secapin-1 displayed the lowest binding scores (−106.9 +/− 7.2 kcal/mol and −101.4 +/− 11.3 kcal/mol, respectively) and the best patterns with stable complexes. The molecular dynamics simulation indicated that the complex of protein DNA-dependent RNA polymerase and the peptide melittin stayed firmly connected and the peptide binding to the receptor protein was stable. The findings of this study provide the evidence of bee peptides as potent antimicrobial agents against sheeppox, goatpox, and lumpy skin disease viruses with no complexity.