Key result
Saquinavir exhibited stable interactions within the 3CLpro active site of PEDV and PDCoV, supported by docking scores of -10.7 and -9.3 kcal/mol and RMSD stabilization at ~2.8 Å.
Why the study?
PDCoV and PEDV cause severe diarrheal disease and high mortality in neonatal piglets, but there are currently no approved antiviral treatments.
Computational screening identifies the HIV protease inhibitor saquinavir as a potential translational lead candidate for inhibiting the 3C-like proteases of porcine coronaviruses.
Saquinavir merits preclinical testing for porcine coronaviruses; leaves open any translational role without experimental validation.
Porcine Delta Coronavirus (PDCoV) and Porcine Epidemic Diarrhea Virus (PEDV) remain major enteric pathogens of swine, responsible for severe diarrheal disease and high mortality among neonatal piglets. Despite intensive control measures, there are currently no approved antiviral treatments. This study applies a One Health -oriented, structure-based drug repurposing approach to identify potential inhibitors of the viral 3C-like proteases (3CLpro), key enzymes required for replication. Ligand-based and structure-based virtual screening were combined with molecular docking , molecular dynamics (MD) simulations (100 ns) , and ADME/Tox profiling using contemporary computational tools (AutoDock Vina 1.2.0, PyRx 0.9.8, YASARA 21.12.24 with AMBER14 force field, SwissADME 2023). Among the screened FDA-approved compounds, saquinavir, a clinically established HIV protease inhibitor, exhibited the most stable interactions within the 3CLpro active site of both viruses, supported by docking scores of –10.7 kcal/mol (PEDV) and –9.3 kcal/mol (PDCoV), and RMSD stabilization at ∼2.8 Å during 100 ns MD simulation. While eravacycline and irinotecan displayed slightly more negative docking energies, saquinavir was prioritized due to its mechanistic relevance as a protease inhibitor, superior stability in MD trajectories, and established safety record. Comparative ADME/Tox analysis indicated predictable pharmacokinetics and manageable bioavailability challenges, amenable to formulation-based improvement. These findings position saquinavir as a translational lead candidate for veterinary antiviral development, bridging human and animal antiviral discovery under the One Health framework. This study also provides a validated computational workflow adaptable for emerging coronaviral infections in livestock and it is an example of how combining veterinary medicine and innovative drug repurposing can open new doors to protect animal health and strengthen food security.
No takes yet. Share an insight, caveat, or question.
A 2025 study studied Porcine Delta Coronavirus (PDCoV) and Porcine Epidemic Diarrhea Virus (PEDV). Saquinavir was evaluated on Binding affinity and stability within the 3CLpro active site. Saquinavir exhibited stable interactions within the 3CLpro active site of PEDV and PDCoV, supported by docking scores of -10.7 and -9.3 kcal/mol and RMSD stabilization at ~2.8 Å.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: