A systems‐level study reveals host‐targeted repurposable drugs against SARS‐CoV‐2 infection

A systems‐level study reveals host‐targeted repurposable drugs against SARS‐CoV‐2 infection

Abstract Understanding the mechanism of SARS‐CoV‐2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID‐19. These were deduced...

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Main Authors: Fangyuan Chen, Qingya Shi, Fen Pei, Andreas Vogt, Rebecca A Porritt, Gustavo Garcia, Angela C Gomez, Mary Hongying Cheng, Mark E Schurdak, Bing Liu, Stephen Y Chan, Vaithilingaraja Arumugaswami, Andrew M Stern, D Lansing Taylor, Moshe Arditi, Ivet Bahar
Format: Article
Language:English
Published: Springer Nature 2021-08-01
Series:Molecular Systems Biology
Subjects:
autophagy
SARS‐CoV‐2‐infected cell transcriptomics
syncytia formation
viral entry
viral–host interactions
Online Access:https://doi.org/10.15252/msb.202110239
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Summary:Abstract Understanding the mechanism of SARS‐CoV‐2 infection and identifying potential therapeutics are global imperatives. Using a quantitative systems pharmacology approach, we identified a set of repurposable and investigational drugs as potential therapeutics against COVID‐19. These were deduced from the gene expression signature of SARS‐CoV‐2‐infected A549 cells screened against Connectivity Map and prioritized by network proximity analysis with respect to disease modules in the viral–host interactome. We also identified immuno‐modulating compounds aiming at suppressing hyperinflammatory responses in severe COVID‐19 patients, based on the transcriptome of ACE2‐overexpressing A549 cells. Experiments with Vero‐E6 cells infected by SARS‐CoV‐2, as well as independent syncytia formation assays for probing ACE2/SARS‐CoV‐2 spike protein‐mediated cell fusion using HEK293T and Calu‐3 cells, showed that several predicted compounds had inhibitory activities. Among them, salmeterol, rottlerin, and mTOR inhibitors exhibited antiviral activities in Vero‐E6 cells; imipramine, linsitinib, hexylresorcinol, ezetimibe, and brompheniramine impaired viral entry. These novel findings provide new paths for broadening the repertoire of compounds pursued as therapeutics against COVID‐19.
ISSN:1744-4292

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