Network Pharmacology Approach to LHQW Indicates Naringenin Targets Several Core Proteins to Regulate Multiple Biological Pathways to Treat and Prevent PRRSV-associated Pneumonia

Background Porcine respiratory and reproductive syndrome(PRRS) is still the most undermine viral disease in hog(Sus scrofa domestica,Sus) farming without effective drug of treatment. This study is aimed to discover its molecular mechanism and provide potential drug targets of LHQW(Lanhua Qingwen) against PRRS. Methods An LHQW target gene set was established from Traditional Chinese Medicine Systems Pharmacology database(TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP),PRRSV(Porcine respiratory and reproductive syndrome virus)-associated pneumonia–related gene set was obtained from 5 disease-gene databases.,Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein-protein interaction (PPI) network were performed to discover the potential proteins.Molecular docking was performed to identify the patterns of interactions between the effective molecules and targeted proteins. Results A total of 509 bioactive ingredients and 255 targets of LHQW as well as 2738 PRRSV-associated pneumonia genes were obtained.The GO and KEGG indicated that LHQW can act by regulating stress response,virus infection and immune response.PPI networks and subnetworks identified 9 core genes.The molecular docking was conducted on the most significant gene MAP kinase-activated protein kinase 3(MAPK3) and other genes of RAC-alpha serine/threonine-protein kinase(AKT1),estrogen receptor 1(ESR1),MAP kinase-activated protein kinase 1(MAPK1),transcription factor p65(RELA) and Heat shock protein HSP 90-alpha(HSP90AA1),which are involved in virus infection,inflammation and oxidative stress pathways.Naringenin can target simultaneously the active pockets of these 6 proteins which exerting potential therapeutic effects in PRRS. Conclusions The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LHQW.Naringenin is a promising molecule for target of MAPK3,AKT1,ESR1,MAPK1,RELA and HSP90AA1 involving in oxidative stress,metabolic regulation,anti-inflammatory and immune defence pathways to treat PRRSV-associated pneumonia.