Orally available ribonucleoside analog with broad anti-viral activity (SARS-CoV-2, RSV, IAV, IBV, HCV, pestivirus, EBOV, CHIKV) in cultures and in vivo.
Originally recognized as a powerful mutagen that preferentially induces AT-to-GC transition in microorganisms, EIDD-1931 (NHC, N4-hydroxycytidine) is an orally available ribonucleoside analog with known anti-viral activity against SARS-CoV, SARS-CoV-2, respiratory syncytial virus (RSV), influenza A & B viruses (IAV & IBV), HCV, pestivirus, bovine viral diarrhoea virus (BVDV), Ebola virus (EBOV), Chikungunya virus (CHIKV), venezuelan equine encephalitis virus (VEEV). NHC effectively reduces RSV and IAVs replication in mice, and exhibts efficacy in a guinea pig IAV transmission model in vivo (100 & 400 mg/kg b.i.d. p.o.). Metabolic studies reveal species-dependent plasma stability.
The New World alphaviruses Venezuelan, Eastern, and Western equine encephalitis viruses (VEEV, EEEV and WEEV, respectively) commonly cause a febrile disease that can progress to meningoencephalitis, resulting in significant morbidity and mortality. To address the need for a therapeutic agent
Antimicrobial agents and chemotherapy, 61(4) (2017-02-01)
Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been
Coronaviruses (CoVs) have emerged from animal reservoirs to cause severe and lethal disease in humans, but there are currently no FDA-approved antivirals to treat the infections. One class of antiviral compounds, nucleoside analogues, mimics naturally occurring nucleosides to inhibit viral
Compounds approved for therapeutic use and in vitro inhibitors of severe acute respiratory syndrome coronavirus (SARS-CoV) were evaluated for inhibition in the mouse SARS-CoV replication model. A hybrid interferon, interferon alpha (IFN-alpha) B/D, and a mismatched double-stranded (ds) RNA interferon
The mutagenic specificty of (oh)4Cyd was examined with T4rII phage mutants which allow for discrimination between AT yields GC and GC yields AT base transitions. AT yields GC transitions were induced with a frequency 1-2 orders of magnitude higher than
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