Broad-spectrum in vitro antiviral activity of ODBG-P-RVn: an orally-available, lipid-modified monophosphate prodrug of remdesivir parent nucleoside (GS-441524)
| Autor: | Nadejda Valiaeva, Payel Chatterjee, Mike Flint, Punya Shrivastava-Ranjan, Robert T. Schooley, James R. Beadle, Karl Y. Hostetler, Joyce Murphy, Christina F. Spiropoulou, Joel M. Montgomery, Michael K. Lo |
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| Rok vydání: | 2021 |
| Předmět: |
ODBG-P-RVn
Physiology Hospitalized patients viruses Observation remdesivir Disease Nipah virus Pharmacology medicine.disease_cause Ebola virus Broad spectrum Medicine Ecology biology hemorrhagic fever virus Prodrug Huh7 cells QR1-502 Infectious Diseases human small airway epithelial cells Drug delivery Vero E6 cells GS-5734 Henipavirus Microbiology (medical) henipavirus filovirus Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Microbiology lipid prodrugs NCI-H358 cells paramyxovirus In vivo remdesivir nucleoside ODBG respiratory viruses antiviral agents Genetics General Immunology and Microbiology SARS-CoV-2 business.industry GS-441524 Cell Biology biology.organism_classification human telomerase reverse-transcriptase (hTERT)-immortalized microvascular endothelial cells (TIME) In vitro business Nucleoside HSAEC1-KT |
| Zdroj: | Microbiology Spectrum, Vol 9, Iss 3 (2021) Microbiology Spectrum |
| DOI: | 10.1101/2021.08.06.455494 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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