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

Mohd Rehan,Saad M Howladar,Khalid Mohammed Kedwa,Firoz Ahmed,Hanadi M Baeissa,Mohammed Y Refai,Mohammad Sarwar Jamal,Torki A Zughaibi

doi:10.3389/fimmu.2021.648250

Abstract

BackgroundThe 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.ResultsWe 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.ConclusionWe 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.

Highlights

The ongoing pandemic by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected more than 168 million people worldwide, causing more than 3.5 million deaths as of 26 May 2021
We employed the later drug development strategy in which the “host response signature network” induced in the SARS-CoV-2 infection was used as targets to repurpose drug molecules to reduce the cytokine storm responsible for severe COVID-19
We found that andrographolide can target four different proteins IL1B, NFkB1, TNF, and IL6 (Table S2A) of the TNF signaling pathway (Figure 1), which might result in blockage of the cytokine storm in COVID-19

Summary

Introduction

The ongoing pandemic by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected more than 168 million people worldwide, causing more than 3.5 million deaths as of 26 May 2021 (https://www.worldometers.info/coronavirus/). Accumulating studies found that an excessively high level of pro-inflammatory cytokines released, called cytokine storm, in response to SARS-CoV-2 infection triggers acute respiratory distress syndrome (ARDS) and multiorgan failure in COVID-19 patients [2, 4]. The most prominent cytokines elevated in the blood plasma of severe COVID-19 patients include TNF, IL-6, IL-8, IL-10, and IL-2 [5, 6]. 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

Methods

Results

Conclusion