Recent advances of enterovirus 71 $$3{\rm C}^{{\rm pro}}$$ 3 C pro targeting Inhibitors
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REVIEW
Recent advances of enterovirus 71 3Cpro targeting Inhibitors Rominah Onintsoa Diarimalala, Meichun Hu, Yanhong Wei and Kanghong Hu*
Abstract With CA16, enterovirus-71 is the causative agent of hand foot and mouth disease (HFMD) which occurs mostly in children under 5 years-old and responsible of several outbreaks since a decade. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death; EV71 has been identified in all severe cases. Therefore, it is actually one of the most public health issues that threatens children’s life. 3Cpro is a protease which plays important functions in EV71 infection. To date, a lot of 3Cpro inhibitors have been tested but none of them has been approved yet. Therefore, a drug screening is still an utmost importance in order to treat and/or prevent EV71 infections. This work highlights the EV71 life cycle, 3Cpro functions and 3Cpro inhibitors recently screened. It permits to well understand all mechanisms about 3Cpro and consequently allow further development of drugs targeting 3Cpro . Thus, this review is helpful for screening of more new 3Cpro inhibitors or for designing analogues of well known 3Cpro inhibitors in order to improve its antiviral activity. Keywords: Enterovirus 71, Enterovirus 71 life cycle, 3Cpro functions, 3Cpro inhibitors, EV71 drugs screening Background Enterovirus 71, belongs to human enterovirus A species, Picornaviridae family, was discovered in a patient with central nervous system (CNS), in California, 1969 [1]. In term of structure, EV71 is a non-enveloped virus with a capsid made up of 60 protomers of envelop proteins and contains a single-stranded RNA positive [2, 3]. Each protomer contains four envelop proteins: VP1– VP2–VP3, located in the external part and are exposed to the host antibodies and cell receptors; and VP4 which is completely hidden in the internal part. The RNA genome is small (7.5 kb) and constituted by 3 parts: Pl, P2 and P3, flanked by 2 UTRs (non-translated regions) located in 5′ and 3′ [4]. Several outbreaks and fatal cases, caused by this virus, make it a major public health issue mainly in *Correspondence: [email protected] National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Sino‑German Biomedical Center, Hubei University of Technology, Wuhan, China
the Asia-Pacific region. Indeed, China has experienced the latest and largest outbreaks with more than 1.7 million cases, 27.000 patients with severe neurological complications and 905 deaths, in 2010 [5]; while a cyclical and seasonal pattern occurs in Sarawak, Japan, Taiwan and Vietnam [6–9]. To manage such infections and epidemics is primordial, and the best way to eradicate this infection is the combination of a valuable vaccine and drugs [10]. Nevertheless,
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