3-Deazaadenosine

Ki: 3.9 μM

3-Deazaadenosine is an inhibitor of S-Adenosylhomocysteine (SAH) hydrolase.

S-Adenosylhomocysteine (SAH) hydrolase can catalyze the reversible hydrolysis of SAH to adenosine and homocysteine. The inhibition of SAH hydrolase result in the intracellular accumulation of SAH, elevating the ratio of SAH to S-adenosylmethionine (SAM) and also inhibiting SAM-dependent methyltransferases.

In vitro: 3-Deazaadenosine showed inhibitory values against the EBO-Z viruses, EBO, and Marburg virus in various cell lines of primate (SW13, Vero 76, FRhL, LLC-MK2, MRC-5, Vero E6) and mouse (BALB/3T3 clone A31) origin. 3-Deazaadenosine at 2 μg/mL could reduce viral replication by 3 logs in a dose-dependent manner. However, there was no further inhibition even with a 100-fold increase in concentration [1].

In vivo: In vehicle control group, adult BALB/c mice lethally infected with mouse-adapted Ebola virus die 5-7 days after infection. In contrast, 3-deazaadenosine treatment initiated on day 0 or 1 led to a dose-dependent protection, with mortality completely prevented at doses around 0.7 mg/kg every 8 h. Moreover, there was significant protection when 3-deazaadenosine treatment was begun on day 2, at which time, the spleen had an average titer of 2 × 10⁶ pfu/g and the liver had 3 × 10⁵ pfu/g virus. Treatment with 3-aeazaadenosine at 2.2 mg/kg initiated on day 3 resulted in 40% survival [1].

Clinical trial: Up to now, 3-deazaadenosine is still in the preclinical development stage.

Reference:
[1] Huggins, Z.  X. Zhang and M. Bray. Antiretroviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit ebola virus in vitro and in a lethal mouse model. Journal of Infectious Diseases 179 (1), S240-S247 (1999).