Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro.
Adenosine Monophosphate
/ analogs & derivatives
Alanine
/ analogs & derivatives
Animals
Antiviral Agents
/ pharmacology
Benzoquinones
/ pharmacology
COVID-19
/ virology
Cell Line
Chlorocebus aethiops
Drug Combinations
Drug Discovery
Drug Synergism
High-Throughput Screening Assays
Humans
Lactams, Macrocyclic
/ pharmacology
Lapatinib
/ pharmacology
Naphthalenes
/ pharmacology
Phenylurea Compounds
/ pharmacology
Pyrazoles
/ pharmacology
RNA, Viral
/ metabolism
SARS-CoV-2
/ drug effects
Vero Cells
Virus Replication
/ drug effects
COVID-19 Drug Treatment
Betacoronavirus
Coronavirus
Lapatinib
OC43
Pharmacologic screening
SARS-CoV-2
Journal
Virology
ISSN: 1096-0341
Titre abrégé: Virology
Pays: United States
ID NLM: 0110674
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
27
07
2021
revised:
18
11
2021
accepted:
19
11
2021
pubmed:
7
12
2021
medline:
7
1
2022
entrez:
6
12
2021
Statut:
ppublish
Résumé
The emergence of SARS-CoV-2 virus has resulted in a worldwide pandemic, but effective antiviral therapies are not widely available. To improve treatment options, we conducted a high-throughput screen to uncover compounds that block SARS-CoV-2 infection. A minimally pathogenic human betacoronavirus (OC43) was used to infect physiologically-relevant human pulmonary fibroblasts (MRC5) to facilitate rapid antiviral discovery in a preclinical model. Comprehensive profiling was conducted on more than 600 compounds, with each compound arrayed across 10 dose points. Our screening revealed several FDA-approved agents that can attenuate both OC43 and SARS-CoV-2 viral replication, including lapatinib, doramapimod, and 17-AAG. Importantly, lapatinib inhibited SARS-CoV-2 RNA replication by over 50,000-fold. Further, both lapatinib and doramapimod could be combined with remdesivir to improve antiviral activity in cells. These findings reveal novel therapeutic avenues that could limit SARS-CoV-2 infection.
Identifiants
pubmed: 34871905
pii: S0042-6822(21)00233-6
doi: 10.1016/j.virol.2021.11.008
pmc: PMC8626825
pii:
doi:
Substances chimiques
Antiviral Agents
0
Benzoquinones
0
Drug Combinations
0
Lactams, Macrocyclic
0
Naphthalenes
0
Phenylurea Compounds
0
Pyrazoles
0
RNA, Viral
0
Lapatinib
0VUA21238F
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
tanespimycin
4GY0AVT3L4
doramapimod
HO1A8B3YVV
Alanine
OF5P57N2ZX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
60-68Subventions
Organisme : NIAID NIH HHS
ID : R01 AI050698
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127370
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM068411
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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