A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm.

Autor:	Rehan M; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Ahmed F; Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.; University of Jeddah Center for Research and Product Development, University of Jeddah, Jeddah, Saudi Arabia., Howladar SM; Department of Biology, College of Science, University of Jeddah, Jeddah, Saudi Arabia., Refai MY; Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia.; University of Jeddah Center for Research and Product Development, University of Jeddah, Jeddah, Saudi Arabia., Baeissa HM; Department of Biochemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia., Zughaibi TA; King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia., Kedwa KM; Hematology Department, Regional Lab Makkah, Haddah, Saudi Arabia., Jamal MS; Integrative Biosciences Center, Wayne State University, Detroit, MI, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Jun 24; Vol. 12, pp. 648250. Date of Electronic Publication: 2021 Jun 24 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.648250
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Rehan, Ahmed, Howladar, Refai, Baeissa, Zughaibi, Kedwa and Jamal.)
Databáze:	MEDLINE
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