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

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 ar...

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Published inMicroorganisms (Basel) Vol. 8; no. 12; p. 1872
Main Authors Holwerda, Melle, V'kovski, Philip, Wider, Manon, Thiel, Volker, Dijkman, Ronald
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 26.11.2020
MDPI
Subjects
Antiinfectives and antibacterials
Antiviral activity
Antiviral agents
Biotechnology
Cell culture
Cell lines
compound screen
Coronaviruses
COVID-19
Cytotoxicity
Drug delivery
Drug development
drug repurposing
Drug resistance
Economic impact
Epidemics
Health care
Impact analysis
Infections
pandemic response box
Pandemics
remdesivir
Replication
Respiratory diseases
Retro-2.1
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Tropical diseases
Vaccines
Viral diseases
Viruses
United States > US
Switzerland
Germany
SARS-CoV-2
Calu-3
drug repurposing
pandemic response box
Retro-2.1
compound screen
remdesivir
Vero E6
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Summary: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.
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These authors contributed equally.
ISSN:2076-2607
2076-2607
DOI:10.3390/microorganisms8121872