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Broad-Spectrum In Vitro Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524).
Lo, Michael K; Shrivastava-Ranjan, Punya; Chatterjee, Payel; Flint, Mike; Beadle, James R; Valiaeva, Nadejda; Murphy, Joyce; Schooley, Robert T; Hostetler, Karl Y; Montgomery, Joel M; Spiropoulou, Christina F.
  • Lo MK; Viral Special Pathogens Branch, Centers for Disease Control and Preventiongrid.416738.f, Department of Health and Human Services, Atlanta, Georgia, USA.
  • Shrivastava-Ranjan P; Viral Special Pathogens Branch, Centers for Disease Control and Preventiongrid.416738.f, Department of Health and Human Services, Atlanta, Georgia, USA.
  • Chatterjee P; Viral Special Pathogens Branch, Centers for Disease Control and Preventiongrid.416738.f, Department of Health and Human Services, Atlanta, Georgia, USA.
  • Flint M; Viral Special Pathogens Branch, Centers for Disease Control and Preventiongrid.416738.f, Department of Health and Human Services, Atlanta, Georgia, USA.
  • Beadle JR; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, USA.
  • Valiaeva N; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, USA.
  • Murphy J; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, USA.
  • Schooley RT; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, USA.
  • Hostetler KY; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, USA.
  • Montgomery JM; Viral Special Pathogens Branch, Centers for Disease Control and Preventiongrid.416738.f, Department of Health and Human Services, Atlanta, Georgia, USA.
  • Spiropoulou CF; Viral Special Pathogens Branch, Centers for Disease Control and Preventiongrid.416738.f, Department of Health and Human Services, Atlanta, Georgia, USA.
Microbiol Spectr ; 9(3): e0153721, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1532984
ABSTRACT
The necessity for intravenous administration of remdesivir confines its utility for treatment of coronavirus disease 2019 (COVID-19) to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524), against viruses that cause diseases of human public health concern, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had activity nearly equivalent to that of remdesivir in primary-like human small airway epithelial cells. Our results warrant in vivo efficacy evaluation of ODBG-P-RVn. IMPORTANCE While remdesivir remains one of the few drugs approved by the FDA to treat coronavirus disease 2019 (COVID-19), its intravenous route of administration limits its use to hospital settings. Optimizing the stability and absorption of remdesivir may lead to a more accessible and clinically potent therapeutic. Here, we describe an orally available lipid-modified version of remdesivir with activity nearly equivalent to that of remdesivir against emerging viruses that cause significant disease, including Ebola and Nipah viruses. Our work highlights the importance of such modifications to optimize drug delivery to relevant and appropriate human tissues that are most affected by such diseases.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Prodrugs / Adenosine / Adenosine Monophosphate / Alanine / COVID-19 Drug Treatment / Nucleosides Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Microbiol Spectr Year: 2021 Document Type: Article Affiliation country: Spectrum.01537-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Prodrugs / Adenosine / Adenosine Monophosphate / Alanine / COVID-19 Drug Treatment / Nucleosides Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Microbiol Spectr Year: 2021 Document Type: Article Affiliation country: Spectrum.01537-21