tetano
Editor, Senior Moderator
Virology
. 2021 Nov 27;566:60-68.
doi: 10.1016/j.virol.2021.11.008. Online ahead of print.
Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro
M H Raymonda[SUP] 1 [/SUP], J H Ciesla[SUP] 1 [/SUP], M Monaghan[SUP] 1 [/SUP], J Leach[SUP] 2 [/SUP], G Asantewaa[SUP] 3 [/SUP], L A Smorodintsev-Schiller[SUP] 4 [/SUP], M M Lutz 4th[SUP] 2 [/SUP], X L Schafer[SUP] 1 [/SUP], T Takimoto[SUP] 2 [/SUP], S Dewhurst[SUP] 2 [/SUP], J Munger[SUP] 5 [/SUP], I S Harris[SUP] 6 [/SUP]
Affiliations
Abstract
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.
Keywords: Betacoronavirus; Coronavirus; Lapatinib; OC43; Pharmacologic screening; SARS-CoV-2.
. 2021 Nov 27;566:60-68.
doi: 10.1016/j.virol.2021.11.008. Online ahead of print.
Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro
M H Raymonda[SUP] 1 [/SUP], J H Ciesla[SUP] 1 [/SUP], M Monaghan[SUP] 1 [/SUP], J Leach[SUP] 2 [/SUP], G Asantewaa[SUP] 3 [/SUP], L A Smorodintsev-Schiller[SUP] 4 [/SUP], M M Lutz 4th[SUP] 2 [/SUP], X L Schafer[SUP] 1 [/SUP], T Takimoto[SUP] 2 [/SUP], S Dewhurst[SUP] 2 [/SUP], J Munger[SUP] 5 [/SUP], I S Harris[SUP] 6 [/SUP]
Affiliations
- PMID: 34871905
- PMCID: PMC8626825
- DOI: 10.1016/j.virol.2021.11.008
Abstract
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.
Keywords: Betacoronavirus; Coronavirus; Lapatinib; OC43; Pharmacologic screening; SARS-CoV-2.