In Silico Discovery of Potential Antiviral Leads Targeting the Canine Parvovirus Type 2 VP2 Capsid Protein

Canine Parvovirus type 2(CPV-2) is the deadliest disease in the puppies, reaching up to 91% mortality in untreated cases. Although a vaccine is available worldwide due to antigenic variation and interference with maternal antibody the efficacy of vaccines is reduced, while there is no FDA-approved antiviral drug is available veterinarians have to rely on symptomatic treatment only. The VP2 capsid protein facilitates viral entry into the host cell by binding with canine transferrin receptor (TfR), while residue Asn93 serves as a major determinant of species-specific recognition, making it a rational target for antiviral drug design This study employed a structure-based virtual screening (SBVS) of approximately 142,000 drug-like molecules from ChEMBL database to find potential inhibitor. Molecular docking simulation centered Asn93 showed superior result of the top ten hits score ranging from -7.4 to -9.5 kcal/mol, outperforming reference molecule by 2.0 to 4.0 kcal/mol. Notably, all ten hits formed direct hydrogen bond with the ND2 side chain atom of the Asn93 residue. Structure-Activity Relationship (SAR) analysis found a common fluorophenyl amino heterocycle pharmacophore in seven of the ten hits. In silico ADMET profiling showed nine out ten compounds have high oral absorption and clean safety profile. Two compounds ChEMBL1794107 and ChEMBL1308064 were prioritized for future experimental validation because of their superior binding energy, clean toxicity profile and geometrically optimal hydrogen bond with Asn93 residue. These findings need further experimental validation and can be a base for future antiviral drug discovery