Molecular docking and network pharmacology highlight salvianolic acids as potential inhibitors and therapeutic agents for COVID-19 treatment

Salvianolic acids have been shown to have therapeutic effects against COVID-19. However, their active compounds and underlying mechanisms have not yet been reported. This study aimed to investigate the effect of salvianolic acids against COVID-19 viral and human target proteins by integrating molecular docking and network pharmacology. Fourteen salvianolic acids were docked against 5 important viral proteins: Spike protein, main protease (Mpro), Helicase, RNA-dependent RNA polymerase (RdRp), and papain-like protease (PLpro). Network pharmacology was performed to identify the active compounds, potential targets and underlying mechanisms of salvianolic acids against COVID-19 human targets. The docking results revealed that 3 active compounds, namely salvianolic acids C, I, and N, bind to and stably interact with the active sites of PLpro, spike protein, Mpro, helicase, and RdRp, with low binding scores. From the network pharmacology results, a total of 7 active compounds and 12 core targets were selected for further analysis. The results of GO and KEGG enrichment analysis indicated that the anti-COVID targets of salvianolic acids are mainly involved in inflammatory processes and could prevent COVID-19 by inhibiting 4 signaling pathways: Coronavirus disease pathway, Cytokine signaling in the immune system, Th17 cell differentiation and Oncostatin signaling pathway. Molecular docking results indicated that all active compounds (Salvianolic acids A, C, I, J, L, N, and Y) could bind to all 12 core targets. However, salvianolic acids C, J, and N were found to be the main active compounds that bind with low (favourable) scores to JAK2, TYK2, and MAPK3 that were found to be the main targets for the treatment of COVID-19. This study revealed the active compounds and potential molecular mechanisms of salvianolic acids against viral and human COVID-19 proteins. These results can serve as a comprehensive reference for studying the mechanism by which salvianolic acids act on COVID-19 and additional research that involves in vitro and in vivo methods.