Nucleozin

Nucleozin Description:EC50: Nucleozin inhibited infection of MDCK cells by the viruses influenza A/WSN/33, H3N2 (clinical isolate) and Vietnam/1194/04 (H5N1) with an EC50 of 0.069±0.003 μM, 0.16±0.01 μM and 0.33±0.04 μM in PRA, respectively [1].
Influenza nucleoprotein is the most abundantly expressed protein during the course of infection with multiple functionalities. In the presence of nucleozin, a potent antagonist of NP accumulation in the nucleus, NP failed to enter the nucleus leading to the virus death [1].
In vitro: Nucleozin was found to effectively inhibite viral growth even when added within 6 h after inoculation of the MDCK cells with the virus, indicating that the antiviral activities of nucleozin reside on post-entry and post-nuclear events, suggesting that multiple processes involving NP may be affected, although only the nuclear import process of NP can be readily observed [1]. However, another in-vitro study demonstrated that the primary target of nucleozin was the viral ribonucleoprotein, not NP, and this work also provided proof of the principle that IAV replication can be effectively inhibited by blocking cytoplasmic trafficking of the viral genome [2].
In vivo: With respect to in vivo antiviral efficacy, mice treated with nucleozin had a considerably higher survival rate after inoculation by influenza A virus H5N1 strain A/Vietnam/1194/04 than untreated controls. Without any treatment, all mice had died 7 d after inoculation. In the nucleozin-treated group, 50% of those receiving two doses of nucleozin (100 μl of 2.3 mg/ml nucleozin) per day for 7 d survived for more than 21 d. The animal study results show that nucleozin protected mice against hypervirulent influenza A H5N1 virus in vivo and thus has the potential to be developed into useful anti-influenza therapeutics [1].
Clinical trial: Up to now, nucleozin is still in the preclinical development stage.
Reference:
[1] Kao RY, Yang D, Lau LS, Tsui WH, Hu L, Dai J, Chan MP, Chan CM, Wang P, Zheng BJ, Sun J, Huang JD, Madar J, Chen G, Chen H, Guan Y, Yuen KY. Identification of influenza A nucleoprotein as an antiviral target. Nat Biotechnol. 2010;28(6):600-5.
[2] Amorim MJ, Kao RY, Digard P. Nucleozin targets cytoplasmic trafficking of viral ribonucleoprotein-Rab11 complexes in influenza A virus infection. J Virol. 2013;87(8):4694-703.