galidesivir and Dengue

Millions of people are infected by the dengue and Zika viruses each year, resulting in significant morbidity and mortality. Galidesivir is an adenosine nucleoside analog that can attenuate flavivirus replication in cell-based assays and animal models of infection. Galidesivir is converted to the triphosphorylated form by host kinases and subsequently incorporated into viral RNA by viral RNA polymerases. This has been proposed to lead to the delayed termination of RNA synthesis. Here, we report direct in vitro testing of the effects of Galidesivir triphosphate on dengue-2 and Zika virus polymerase activity. Galidesivir triphosphate was chemically synthesized, and inhibition of RNA synthesis followed using a dinucleotide-primed assay with a homopolymeric poly(U) template. Galidesivir triphosphate was equipotent against dengue-2 and Zika polymerases, with IC

Topics: Adenosine; Animals; Antiviral Agents; Dengue; Nucleotidyltransferases; RNA, Viral; Zika Virus; Zika Virus Infection

Topics: Adenine; Adenosine; Antiviral Agents; Benzamides; Chloroquine; Communicable Diseases, Emerging; Cyclosporins; Cytosine; Dengue; Drug Approval; Drug Design; Erlotinib Hydrochloride; Hemorrhagic Fever, Ebola; Humans; Imatinib Mesylate; Indoles; Organophosphonates; Piperazines; Purine Nucleosides; Pyrimidines; Pyrroles; Pyrrolidines; Quinazolines; Sunitinib; Viruses