Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

Selwyn J. Hurwitz; Ramyani De; Julia C. LeCher; Jessica A. Downs-Bowen; Shu Ling Goh; Keivan Zandi; Tamara McBrayer; Franck Amblard; Dharmeshkumar Patel; James J. Kohler; Manoj Bhasin; Brian S. Dobosh; Vikas Sukhatme; Rabindra M. Tirouvanziam; Raymond F. Schinazi

doi:10.3390/v16040651

Viruses (Apr 2024)

Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections

Selwyn J. Hurwitz,
Ramyani De,
Julia C. LeCher,
Jessica A. Downs-Bowen,
Shu Ling Goh,
Keivan Zandi,
Tamara McBrayer,
Franck Amblard,
Dharmeshkumar Patel,
James J. Kohler,
Manoj Bhasin,
Brian S. Dobosh,
Vikas Sukhatme,
Rabindra M. Tirouvanziam,
Raymond F. Schinazi

Affiliations

Selwyn J. Hurwitz: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Ramyani De: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Julia C. LeCher: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Jessica A. Downs-Bowen: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Shu Ling Goh: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Keivan Zandi: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Tamara McBrayer: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Franck Amblard: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Dharmeshkumar Patel: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
James J. Kohler: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA
Manoj Bhasin: Center for Cystic Fibrosis & Airways Disease Research, Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Emory University and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA
Brian S. Dobosh: Center for Cystic Fibrosis & Airways Disease Research, Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Emory University and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA
Vikas Sukhatme: Morningside Center for Innovative and Affordable Medicine, Departments of Medicine and Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA
Rabindra M. Tirouvanziam: Center for Cystic Fibrosis & Airways Disease Research, Division of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Emory University and Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA 30322, USA
Raymond F. Schinazi: Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA

DOI: https://doi.org/10.3390/v16040651
Journal volume & issue: Vol. 16, no. 4
p. 651

Abstract

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Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC50, were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC50 was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound Cmax/EC50 ≥ 6.8 in Calu-3 or Caco-2 cells. EC50 of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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