Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro

Melle Holwerda; Philip V'kovski; Manon Wider; Volker Thiel; Ronald Dijkman

doi:10.3390/microorganisms8121872

Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro

Microorganisms. 2020 Nov 26;8(12):1872. doi: 10.3390/microorganisms8121872.

Authors

Melle Holwerda^{1

2

3

4}, Philip V'kovski^{1

2

3}, Manon Wider³, Volker Thiel^{1

2}, Ronald Dijkman^{1

2

3}

Affiliations

¹ Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland.
² Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
³ Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland.
⁴ Graduate School for Molecular Cell Biology, University of Bern, 3012 Bern, Switzerland.

Abstract

With over 50 million currently confirmed cases worldwide, including more than 1.3 million deaths, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, limited prophylactic or therapeutic intervention options are available against SARS-CoV-2. In this study, 400 compounds from the antimicrobial "pandemic response box" library were screened for inhibiting properties against SARS-CoV-2. An initial screen on Vero E6 cells identified five compounds that inhibited SARS-CoV-2 replication. However, validation of the selected hits in a human lung cell line highlighted that only a single compound, namely Retro-2.1, efficiently inhibited SARS-CoV-2 replication. Additional analysis revealed that the antiviral activity of Retro-2.1 occurs at a post-entry stage of the viral replication cycle. Combined, these data demonstrate that stringent in vitro screening of preselected compounds in multiple cell lines refines the rapid identification of new potential antiviral candidate drugs targeting SARS-CoV-2.

Keywords: Calu-3; Retro-2.1; SARS-CoV-2; Vero E6; compound screen; drug repurposing; pandemic response box; remdesivir.

Abstract

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