Background The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality. This work uses a rational computational strategy to identify the existing drug molecules to target host pathways to reduce the cytokine storm. Results We used a “ host response signature network ” consist of 36 genes induced by SARS-CoV-2 infection and associated with cytokine storm. In order to attenuate the cytokine storm, potential drug molecules were searched against “host response signature network” . Our study identified that drug molecule andrographolide, naturally present in a medicinal plant Andrographis paniculata , has the potential to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway responsible for cytokine storm in COVID-19 patients. The molecular docking method showed the binding of andrographolide with TNF and covalent binding with NFkB1 proteins of the TNF signaling pathway. Conclusion We used a rational computational approach to repurpose existing drugs targeting host immunomodulating pathways. Our study suggests that andrographolide could bind with TNF and NFkB1 proteins, block TNF-induced cytokine storm in COVID-19 patients, and warrant further experimental validation.
【저자키워드】 COVID-19, SARS-CoV-2, Cytokine storm, molecular docking, systems bioinformatics, drug-repurposing, andrographolide, TNF signaling pathway, 【초록키워드】 Cytokine storm, coronavirus, SARS-COV-2 infection, cytokine, Proteins, host response, Betacoronavirus, andrographolide, Protein, pathway, hyper-inflammation, signaling pathway, respiratory, COVID-19 patients, binding, fatality, TNF, Pathways, reason for, experimental validation, severe COVID-19 patients, multi-organ failure, causative pathogen, covalent binding, NFkB1, immunomodulating, Host, approach, TNF signaling, Result, responsible, identify, searched, cause, reduce, drugs targeting, attenuate, severe COVID-19 patient, the cytokine storm, 【제목키워드】 drug, andrographolide, storm, Potential, Identified, Suppressing,