N4-Hydroxycytidine | Novel antiviral

N⁴-Hydroxycytidine (3258-02-4) was originally identified as a mutagen effecting AT to GC base-pair transitions.¹ It has also been found to have antiviral properties against a broad range of viruses including hepatitis C², norovirus³, Ebola virus⁴, Chikungunya virus⁵, influenza and respiratory syncytial viruses⁶, and importantly, coronaviruses.^7,8 N⁴-hydroxycytidine is the active molecule in the antiviral pro-drug clinical candidate EIDD-2801.⁹

References/Citations:

1) Janion and Glickman (1980), N4-hydroxycytidine: a mutagen specific for AT to GC transitions; Mutat. Res., 72 43
2) Stuyver et al. (2003), Ribonucleotide analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture; Antimicrob. Agents Chemother., 47 244
3) Costantini et al. (2012), Antiviral activity of nucleoside analogues against norovirus; Antivir. Ther., 17 981
4) Reynard et al. (2015), Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication; Viruses, 7 6233
5) Ehteshami et al. (2017), Characterization of ß-D-N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus; Antimicrob. Agents Chemother., 61 e02395-16
6) Yoon et al. (2018), Orally efficacious broad-spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses; Antimicrob. Agents Chemother., 62 e00766-18
7) Barnard et al. (2004), Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and beta-D-N4-hydroxycytidine; Antivir. Chem. Chemother., 15 15
8) Pyrc et al. (2006), Inhibition of human coronavirus NL63 infection at early stages of the replication cycle; Antimicrob. Agents Chemother., 50 2000
9) Toots et al. (2019), Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia; Sci. Transl. Med., 11 eaax5866