Study of kaempferol in the treatment of COVID-19 combined with Chikungunya co-infection by network pharmacology and molecular docking technology

Chikungunya (CHIK) patients may be vulnerable to coronavirus disease (COVID-19). However, presently there are no anti-COVID-19/CHIK therapeutic alternatives available. The purpose of this research was to determine the pharmacological mechanism through which kaempferol functions in the treatment of COVID-19-associated CHIK co-infection. We have used a series of network pharmacology and computational analysis-based techniques to decipher and define the binding capacity, biological functions, pharmacological targets, and treatment processes in COVID-19-mediated CHIK co-infection. We identified key therapeutic targets for COVID-19/CHIK, including TP53, MAPK1, MAPK3, MAPK8, TNF, IL6 and NFKB1. Gene ontology, molecular and upstream pathway analysis of kaempferol against COVID-19 and CHIK showed that DEGs were confined mainly to the cytokine-mediated signalling pathway, MAP kinase activity, negative regulation of the apoptotic process, lipid and atherosclerosis, TNF signalling pathway, hepatitis B, toll-like receptor signaling, IL-17 and IL-18 signaling pathways. The study of the gene regulatory network revealed several significant TFs including KLF16, GATA2, YY1 and FOXC1 and miRNAs such as let-7b-5p, mir-16-5p, mir-34a-5p, and mir-155-5p that target differential-expressed genes (DEG). According to the molecular coupling results, kaempferol exhibited a high affinity for 5 receptor proteins (TP53, MAPK1, MAPK3, MAPK8, and TNF) compared to control inhibitors. In combination, our results identified significant targets and pharmacological mechanisms of kaempferol in the treatment of COVID-19/CHIK and recommended that core targets be used as potential biomarkers against COVID-19/CHIK viruses. Before conducting clinical studies for the intervention of COVID-19 and CHIK, kaempferol might be evaluated in wet lab tests at the molecular level.