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Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS-CoV-2 in vitro.
Raymonda, M H; Ciesla, J H; Monaghan, M; Leach, J; Asantewaa, G; Smorodintsev-Schiller, L A; Lutz, M M; Schafer, X L; Takimoto, T; Dewhurst, S; Munger, J; Harris, I S.
  • Raymonda MH; Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
  • Ciesla JH; Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
  • Monaghan M; Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
  • Leach J; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
  • Asantewaa G; Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
  • Smorodintsev-Schiller LA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
  • Lutz MM; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
  • Schafer XL; Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
  • Takimoto T; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
  • Dewhurst S; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA.
  • Munger J; Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. Elect
  • Harris IS; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: isaac_harris@urmc.rochester.edu.
Virology ; 566: 60-68, 2022 01.
Article in English | MEDLINE | ID: covidwho-1537115
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine Monophosphate / Alanine / Lapatinib / SARS-CoV-2 / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Journal: Virology Year: 2022 Document Type: Article Affiliation country: J.virol.2021.11.008

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Adenosine Monophosphate / Alanine / Lapatinib / SARS-CoV-2 / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Journal: Virology Year: 2022 Document Type: Article Affiliation country: J.virol.2021.11.008