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.
【저자키워드】 SARS-CoV-2, coronavirus, Betacoronavirus, OC43, Lapatinib, Pharmacologic screening, 【초록키워드】 Treatment, SARS-CoV-2, antiviral therapy, Antiviral, SARS-COV-2 infection, Remdesivir, SARS-CoV-2 virus, antiviral activity, Betacoronavirus, Replication, cells, viral replication, therapeutic, SARS-CoV-2 RNA, OC43, compounds, dose, Lapatinib, worldwide pandemic, Compound, pathogenic, SARS-CoV-2 viral replication, Pharmacologic, infect, fibroblast, effective, limit, human betacoronavirus, Comprehensive, 17-AAG, doramapimod, IMPROVE, was used, inhibited, conducted, facilitate, attenuate, 【제목키워드】 SARS-CoV-2, Antiviral, in vitro, Lapatinib, Pharmacologic, reveal,