Anthracyclines inhibit SARS-CoV-2 infection

Zhen Wang; Qinghua Pan; Ling Ma; Jianyuan Zhao; Fiona McIntosh; Zhenlong Liu; Shilei Ding; Rongtuan Lin; Shan Cen; Andrés Finzi; Chen Liang

doi:10.1016/j.virusres.2023.199164

Anthracyclines inhibit SARS-CoV-2 infection

Virus Res. 2023 Sep:334:199164. doi: 10.1016/j.virusres.2023.199164. Epub 2023 Jun 28.

Authors

Zhen Wang¹, Qinghua Pan², Ling Ma³, Jianyuan Zhao³, Fiona McIntosh⁴, Zhenlong Liu¹, Shilei Ding⁵, Rongtuan Lin⁶, Shan Cen³, Andrés Finzi⁵, Chen Liang⁷

Affiliations

¹ Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada.
² Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
³ Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, People's Republic of China.
⁴ Research Institute of the McGill University Health Centre, McGill International TB Centre, Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
⁵ Centre de Recherche du CHUM, Montreal, Quebec, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada.
⁶ Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
⁷ Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. Electronic address: chen.liang@mcgill.ca.

Abstract

Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks. We have screened a library of microbial metabolites to discover new SARS-CoV-2 inhibitors. To facilitate this screening effort, we generated a recombinant SARS-CoV-2 Delta variant carrying the nano luciferase as a reporter for measuring viral infection. Six compounds were found to inhibit SARS-CoV-2 at the half maximal inhibitory concentration (IC50) below 1 μM, including the anthracycline drug aclarubicin that markedly reduced viral RNA-dependent RNA polymerase (RdRp)-mediated gene expression, whereas other anthracyclines inhibited SARS-CoV-2 by activating the expression of interferon and antiviral genes. As the most commonly prescribed anti-cancer drugs, anthracyclines hold the promise of becoming new SARS-CoV-2 inhibitors.

Keywords: Anthracycline; Interferon; Microbial metabolites; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthracyclines / pharmacology
Antiviral Agents / metabolism
Antiviral Agents / pharmacology
COVID-19*
Humans
SARS-CoV-2

Substances

Anthracyclines
nirmatrelvir and ritonavir drug combination
Antiviral Agents

Supplementary concepts

SARS-CoV-2 variants