Network pharmacology approach to reveals therapeutic mech-anism of traditional plants formulation used by Malaysia in-digenous ethnics in coronaviruses infection

Network pharmacology analysis can act as a strategy to identify the pharmacological effect of plant-based bioactive compounds against coronavirus diseases. This study aimed to investigate the potential pharmacological mechanism of a local ethnomedicine (Costus speciosus, Hibiscus rosa-sinensis and Phyllanthus niruri) of Northern Borneo against coronaviruses known as CHP. Compounds in CHP were extracted from databases and screened for their oral bioavailability and drug-likeness before a compound-target network was built. Furthermore, the protein-protein interaction network and pathway enrichment were constructed and analyzed. A compound-target network consisting of 48 putative bioactive compounds targeting 587 candidate genes was identified. A total of 186 coronavirus-related genes were extracted and TP53, STAT3, HSP90AA1, STAT1, and EP300 were predicted to be the key targets. Notably, mapping of these target genes into the target-pathway network illustrated that functional enrichment was on viral infection and regulation of inflammation pathways. Urinatetralin is predicted, for the first time, as a bioactive compound that solely targets STAT3. The results from this study indicate that compounds present in CHP employ STAT3 and its connected pathways as the mechanism of action against coronaviruses. In conclusion, urinatetralin should be further investigated for its potential application against coronavirus infections.