Broad-Spectrum <i>In Vitro</i> Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524)
Michael K. Lo, Punya Shrivastava-Ranjan, Payel Chatterjee, Mike Flint, James R. Beadle, Nadejda Valiaeva, Joyce Murphy, Robert T. Schooley, Karl Y. Hostetler, Joel M. Montgomery, Christina F. Spiropoulou
Abstract
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.