A systems-level study reveals host-targeted repurposable drugs against SARS-CoV-2 infection.
Mol Syst Biol
; 17(8): e10239, 2021 08.
Article
in English
| MEDLINE | ID: covidwho-1335457
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Drug Evaluation, Preclinical
/
Virus Internalization
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Traditional medicine
Limits:
Animals
/
Humans
Language:
English
Journal:
Mol Syst Biol
Journal subject:
Molecular Biology
/
Biotechnology
Year:
2021
Document Type:
Article
Affiliation country:
Msb.202110239
Similar
MEDLINE
...
LILACS
LIS