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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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.
AbstractList 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.
Author V'kovski, Philip
Dijkman, Ronald
Holwerda, Melle
Wider, Manon
Thiel, Volker
AuthorAffiliation 4 Graduate School for Molecular Cell Biology, University of Bern, 3012 Bern, Switzerland
2 Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
1 Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; melle.holwerda@vetsuisse.unibe.ch (M.H.); Philip.vkovski@ifik.unibe.ch (P.V.); volker.thiel@vetsuisse.unibe.ch (V.T.)
3 Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland; manon.wider@ifik.unibe.ch
AuthorAffiliation_xml – name: 1 Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland; melle.holwerda@vetsuisse.unibe.ch (M.H.); Philip.vkovski@ifik.unibe.ch (P.V.); volker.thiel@vetsuisse.unibe.ch (V.T.)
– name: 4 Graduate School for Molecular Cell Biology, University of Bern, 3012 Bern, Switzerland
– name: 2 Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland
– name: 3 Institute for Infectious Diseases, University of Bern, 3001 Bern, Switzerland; manon.wider@ifik.unibe.ch
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33256227$$D View this record in MEDLINE/PubMed
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Keywords SARS-CoV-2
Calu-3
drug repurposing
pandemic response box
Retro-2.1
compound screen
remdesivir
Vero E6
Language English
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Snippet With over 50 million currently confirmed cases worldwide, including more than 1.3 million deaths, the severe acute respiratory syndrome coronavirus 2...
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SubjectTerms 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
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Title Identification of an Antiviral Compound from the Pandemic Response Box that Efficiently Inhibits SARS-CoV-2 Infection In Vitro
URI https://www.ncbi.nlm.nih.gov/pubmed/33256227
https://www.proquest.com/docview/2465901719
https://search.proquest.com/docview/2466033197
https://pubmed.ncbi.nlm.nih.gov/PMC7760777
https://doaj.org/article/44c18b20a7b94d4b93f2a2f22c218457
Volume 8
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