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Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model.
Cáceres, C Joaquín; Cardenas-Garcia, Stivalis; Carnaccini, Silvia; Seibert, Brittany; Rajao, Daniela S; Wang, Jun; Perez, Daniel R.
  • Cáceres CJ; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Cardenas-Garcia S; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Carnaccini S; Tifton Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, Tifton, GA, USA.
  • Seibert B; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Rajao DS; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
  • Wang J; Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, USA. junwang@pharmacy.arizona.edu.
  • Perez DR; Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA. dperez1@uga.edu.
Sci Rep ; 11(1): 9609, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1217711
Preprint
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ABSTRACT
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 105 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 103 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Sulfonic Acids / Carbonates / Angiotensin-Converting Enzyme 2 / COVID-19 Drug Treatment / Leucine Type of study: Experimental Studies / Observational study / Prognostic study Limits: Animals Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-89013-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Sulfonic Acids / Carbonates / Angiotensin-Converting Enzyme 2 / COVID-19 Drug Treatment / Leucine Type of study: Experimental Studies / Observational study / Prognostic study Limits: Animals Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-89013-w