Broad-Spectrum In Vitro Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524).
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.
Keywords
Ebola virus; GS-441524; GS-5734; HSAEC1-KT; Huh7 cells; NCI-H358 cells; Nipah virus; ODBG; ODBG-P-RVn; SARS-CoV-2; Vero E6 cells; antiviral agents; filovirus; hemorrhagic fever virus; henipavirus; human small airway epithelial cells; human telomerase reverse-transcriptase (hTERT)-immortalized microvascular endothelial cells (TIME); lipid prodrugs; paramyxovirus; remdesivir; remdesivir nucleoside; respiratory viruses
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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