The outbreak of Sheep and goat pox (SGP) viral infections have increasingly been reported despite vaccinating the majority of sheep populations in Iran. The objective of this study was to predict the impacts of the SGP P32/envelope variations on the binding with host receptors as a candidate tool to assess this outbreak. The targeted gene was amplifed in a total of 101 viral samples, and the PCR products were subjected to Sanger sequencing. The polymorphism and phylogenetic interactions of the identifed variants were assessed. Molecular docking was performed between the identifed P32 variants and the host receptor and the efects of these variants were evaluated. Eighteen variations were identifed in the investigated P32 gene with variable silent and missense efects on the envelope protein. Five groups (G1–G5) of amino acid variations were identifed. While there were no amino acid variations in the G1 (wild-type) viral protein, G2, G3, G4, and G5 proteins had seven, nine, twelve, and fourteen SNPs, respectively. Based on the observed amino acid substitutions, multiple distinct phylogenetic places were occupied from the identifed viral groups. Dramatic alterations were identifed between G2, G4, and G5 variants with their proteoglycan receptor, while the highest binding was revealed between goatpox G5 variant with the same receptor. It was suggested that the higher severity of goatpox viral infection originated from its higher afnity to bind with its cognate receptor. This frm binding may be explained by the observed higher severity of the SGP cases from which G5 samples were isolated.

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