Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections-Reference-Cited by-同舟云学术

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

Published:2024-04-22 Issue:4 Volume:16 Page:651
ISSN:1999-4915
Container-title:Viruses
language:en
Short-container-title:Viruses

Author:

Hurwitz Selwyn J.¹,De Ramyani¹,LeCher Julia C.¹^ORCID,Downs-Bowen Jessica A.¹^ORCID,Goh Shu Ling¹,Zandi Keivan¹,McBrayer Tamara¹,Amblard Franck¹,Patel Dharmeshkumar¹^ORCID,Kohler James J.¹,Bhasin Manoj²,Dobosh Brian S.²,Sukhatme Vikas³,Tirouvanziam Rabindra M.²^ORCID,Schinazi Raymond F.¹^ORCID

Affiliation:

1. 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

2. 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

3. Morningside Center for Innovative and Affordable Medicine, Departments of Medicine and Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA

Abstract

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.

Publisher

MDPI AG

Link

https://www.mdpi.com/1999-4915/16/4/651/pdf

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