Computational identification of potential inhibitors for dominant proteins in Viperidae snakes from FDA-approved drugs

• 1823 FDA-approved drugs screened against viper venom toxins via in silico tools • Key targets: Atrolysin C, PDE, HYAL, and LAAOs form dominant Viper toxins • Risdiplam, Bexarotene, and Pacritinib showed strong binding with Atrolysin C • Capmatinib and Belumosudil effectively bind PDE and HYAL enzymes • ADMET profiling indicates favourable drug properties for further development Snake venom toxins play crucial roles in both direct and indirect pathophysiological effects following envenomation, with limited approved chemotherapeutics available. Hence, this study identifies and elucidates potent inhibitors of specific viper venom toxins using computational biology approaches. A total of 1823 FDA-approved drugs were retrieved from DrugBank. Four prominent viper venom enzymes, Atrolysin C, Phosphodiesterase (PDE), Hyaluronidase (HYAL), and L-amino acid oxidases (LAAOs), were obtained from the Protein Data Bank. The PyRx software was used to prepare the drugs as ligands and proteins as macromolecules. Molecular dynamics simulation was performed on the potential protein-ligand complexes. ADMET studies were conducted using the AdmetLab 3.0 server. Results showed that fifteen ligands exhibited lower binding affinity scores ranging from -12.7 kcal/mol to -9.1 kcal/mol, compared to the controls (-9.2 kcal/mol to -5.4 kcal/mol). Risdiplam, Bexarotene, and Pacritinib formed more stable complexes with Atrolysin C than the control. Capmatinib and Belumosudil were identified to form commendable complexes with PDE and HYAL. Selinexor displayed less stability but a more favourable binding affinity and interaction with LAAOs. The ADMET profiled the promising drugs with favourable pharmacokinetic properties. Therefore, the lead drugs are recommended as potent inhibitors of prominent viper venom toxins and for further development.