Introduction:
Porcine delta coronavirus (PDCoV) and porcine epidemic diarrhoea virus (PEDV) continue to pose a threat to global swine health, animal welfare, and food security. These enteric coronaviruses are associated with severe diarrhoea, dehydration, and high mortality in neonatal piglets. Despite significant economic losses, no antiviral treatments are currently approved, and vaccine control remains suboptimal due to viral evolution and incomplete protection. Repurposing clinically approved drugs that target conserved viral proteases represents a rapid and cost-effective therapeutic strategy aligned with the principles of One Health.

Methods:
We retrieved high-resolution crystal structures of PDCoV and PEDV 3CL proteases (PDB IDs: 4XFQ and 8E7C). Following the validation of docking protocols using AutoDock Vina and PyRx software, compound libraries from DrugBank and ZINC15 were virtually screened. Top-ranking hits were prioritised based on docking scores and interaction profiles. These candidates were subjected to molecular dynamics simulations to evaluate complex stability over time. In silico pharmacokinetic and toxicity predictions were performed using SwissADME and pkCSM tools to assess oral bioavailability and safety profiles.

Results:
Saquinavir, an FDA-approved HIV protease inhibitor, demonstrated consistently favourable docking interactions with conserved catalytic residues in the viral protease active sites. Molecular dynamics simulations confirmed the stability of binding conformations over 100 ns, supporting the robustness of the predicted interactions. Pharmacokinetic profiling indicated acceptable oral absorption and low predicted toxicity.

Conclusions:
This integrated virtual screening and simulation pipeline identifies saquinavir as a promising repurposed candidate against porcine enteric coronaviruses. These findings justify urgent in vitro validation and illustrate how drug repurposing can accelerate antiviral discovery in veterinary medicine within a One Health framework.