NITD008 (7-Deaza-2'-C-acetylene-adenosine) is a potent and selective adenosine nucleoside inhibitor.NITD008 is an adenosine nucleoside analog with broad-spectrum antiviral activity that inhibits dengue, animal cupripoxvirus, and Zika virus.

DENV-2:0.64 μM (EC50), HCV 1b:0.11 μM (EC50)

NITD008 exhibits potent inhibition against various viruses, including Dengue virus (DENV), West Nile virus, yellow fever virus, and Poissan virus. In the case of DENV-2, NITD008 inhibits the virus in a dose-responsive manner, with an EC50 value of 0.64 μM. Treatment with 9 μM of the compound results in a reduction in viral titer by >104-fold[1].Furthermore, NITD008 also demonstrates inhibitory activity against a luciferase-reporting replicon of hepatitis C virus (HCV, genotype 1b), a member of the genus Hepacivirus, with an EC50 value of 0.11 μM[1].

NITD008, with good pharmacokinetic properties, is orally bioavailable. The formulation using 6 N HCl (1.5 equimolar amount), 1 N NaOH (pH adjusted to 3.5), and 100 mM citrate buffer (pH 3.5) yields the best pharmacokinetic parameters. Following intravenous (i.v.) injection, NITD008 demonstrates a high volume of distribution (3.71 L/kg) and low systemic clearance (31.11 mL/min per kg), resulting in a long elimination half-life (t1/2=4.99 h).
After oral dosing, NITD008 is rapidly absorbed (time of peak plasma concentration=0.5 h), reaching a maximal plasma concentration of 3 μM, with a bioavailability of 48%. When administered immediately after viral infection, a dose of 1 mg/kg of NITD008 does not reduce mortality, but treatment with 3 mg/kg provides partial protection, and doses of ≥10 mg/kg completely protect infected mice from death. NITD008 effectively suppresses peak viremia, reduces cytokine elevation, and prevents mortality in the infected mice[1].