Based on Molecular Docking, Molecular Dynamics Simulation and MM/PB(GB)SA to Study Potential Inhibitors of PRRSV‐Nsp4

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the most serious infectious immunosuppressive diseases in the world. The nonstructural protein Nsp4 can be used as an ideal target for anti‐PRRSV replication inhibitors. However, little is known about potential inhibitors that target Nsp4 to affect PRRSV replication. The purpose of this study was to screen potential natural inhibitors that affect PRRSV replication by inhibiting Nsp4. Five compounds with strong binding affinity to Nsp4 were selected by structure‐based molecular docking method. The complexes of naringin dihydrochalcone (NDC), agathisflavone (AGT), and amentoflavone (AMF) with Nsp4 were stable throughout the molecular dynamics simulation. According to MM/PBSA analysis, the free energies of binding of NDC, AGT, and AMF to Nsp4 were less than—30 Kcal/mol. In conclusion, these three compounds are worthy of further investigation as novel inhibitors of PRRSV. This study provides a theoretical basis for the development of anti‐PRRSV natural drugs.