Interleukin-10 as Covid-19 biomarker targeting KSK and its analogues: Integrated network pharmacology

Abstract

COVID-19 caused by the SARS-CoV-2 virus is widespread in all regions, and it disturbs host immune system functioning leading to extreme inflammatory reaction and hyperactivation of the immune response. Kabasura Kudineer (KSK) is preventive medicine against viral infections and a potent immune booster for inflammation-related diseases. We hypothesize that KSK and KSK similar plant compounds, might prevent or control the COVID-19 infection in the human body. 1,207 KSK and KSK similar compounds were listed and screened via the Swiss ADME tool and PAINS Remover; 303 compounds were filtered including active and similar drug compounds. The targets were retrieved from similar drugs of the active compounds of KSK. Finally, 573 genes were listed after several screening steps. Next, network analysis was performed to finalize the potential target gene: construction of protein-protein interaction of 573 genes using STRING, identifying top hub genes in Cytoscape plug-ins (MCODE and cytoHubba). These ten hub genes play a crucial role in the inflammatory response. Target-miRNA interaction was also constructed using the miRNet tool to interpret miRNAs of the target genes and their functions. Functional annotation was done via DAVID to gain a complete insight into the mechanism of the enriched pathways and other diseases related to the given target genes. In Molecular Docking analysis, IL10 attained top rank in Target-miRNA interaction and also the gene formed prominent exchanges with an excellent binding score (> = -8.0) against 19 compounds. Among them, Guggulsterone has an acute affinity score of -8.8 for IL10 and exhibits anti-inflammatory and immunomodulatory properties. Molecular Dynamics simulation study also performed for IL10 and the interacting ligand compounds using GROMACS. Finally, Guggulsterone will be recommended to enhance immunity against several inflammatory diseases, including COVID19.

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway

“…IL-10 is a cytokine encoded by the IL-10 gene. In the human body, IL-10 is mainly produced by immune cells[ 16 ] and is associated with various cancers such as gastric[ 15 ], colon[ 17 ], breast[ 18 ], pancreatic[ 19 ], and cervical[ 20 ] cancers. IL-10 can regulate the JAK1/STAT3 signaling pathway[ 21 ] and extracellular signal regulation[ 22 ] and affects the expression of downstream molecules.…”