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. 3{rm C}^{{rm pro}} is a protease which plays important functions in EV71 infection. To date, a lot of 3{rm C}^{{rm pro}} 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, 3{rm C}^{{rm pro}} functions and 3{rm C}^{{rm pro}} inhibitors recently screened. It permits to well understand all mechanisms about 3{rm C}^{{rm pro}} and consequently allow further development of drugs targeting 3{rm C}^{{rm pro}}. Thus, this review is helpful for screening of more new 3{rm C}^{{rm pro}} inhibitors or for designing analogues of well known 3{rm C}^{{rm pro}} inhibitors in order to improve its antiviral activity.
Highlights
Enterovirus 71, belongs to human enterovirus A species, Picornaviridae family, was discovered in a patient with central nervous system (CNS), in California, 1969 [1]
Non‐peptidyl compound: DC07090 Recently identified as novel small potent molecule 3C inhibitor, it is a non-peptidyl compound designed by docking-based virtual screening and able to bind with 3C through its binding site and reversible inhibits its protease activity at 50% Effective Concentration (EC50) = 22.09 ± 1.07 μM
We summarized several classes of compound recently screened and rupintrivir which is the drug of reference against 3C protease (3Cpro)
Summary
Enterovirus 71, belongs to human enterovirus A species, Picornaviridae family, was discovered in a patient with central nervous system (CNS), in California, 1969 [1]. The compounds 8v, 8w and 8x were exhibiting the most potent antiviral activity against enterovirus 71 with EC50 = 1.32 ± 0.26, 1.88 ± 0.35 and 1.52 ± 0.31 μM respectively Those compounds should be more improved and studied in order to contribute for EV71 drug discovery which is currently in need [42]. Non‐peptidyl compound: DC07090 Recently identified as novel small potent molecule 3C inhibitor, it is a non-peptidyl compound designed by docking-based virtual screening and able to bind with 3C through its binding site and reversible inhibits its protease activity at EC50 = 22.09 ± 1.07 μM. Researchers used them as a base of drug and dietary supplement in several diseases [44] They present an attractive therapy for Enterovirus 71 due to their low toxicity towards host cells and their strong antiviral activity. Further investigation must be conducted about silencing gene strategy within using 3Cpro as target [49]
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