Ebola virus VP35 has novel NTPase and helicase-like activities

Shu, Ting; Gan, Tianyu; Bai, Peng; Wang, Xiaotong; Qian, Qi; Zhou, Hui; Cheng, Qi; Qiu, Yang; Yin, Lei; Zhong, Jin; Zhou, Xi

Virus-encoded helicases have long been considered as potential targets for antivirals due to their importance in viral replication (35) . Previous studies have reported that GuHCl can effectively inhibit the helicase activities of enterovirus 2C and human norovirus NS3, as well as the replication of enterovirus and human norovirus (22, (64) (65) (66) . Similarly, using the stable EBOV minigenome as the model, we also found that the helicase-like activity of VP35 and the replication of EBOV minigenome in cells can be significantly inhibited with negligible cell toxicity by GuHCl. Guanidines are ubiquitously present in nature, and can function as mediators of specific non-covalent binding in various catalytic processes (64, 67) . Due to the physicochemical characteristics, guanidine derivatives have been used for drug development against diverse diseases, some of which are potential antivirals against hepatitis C virus (HCV), human immunodeficiency virus (HIV), and flaviviruses (64, (67) (68) (69) , and GuHCl is a U.S. FDA-approved small compound drug for the treatment of Eaton-Lambert syndrome (36, 37) . Considering the presence of multiple guanidine derivatives, the modification and screening of various guanidinecontaining compounds can probably identify antiviral compounds with better inhibitory effects on EBOV VP35 and EBOV replication.