Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening

Ma, Guanghui; Ye, Yan; Zhang, Dan; Xu, Xin; Si, Pei; Peng, Jiantang; Xiao, Yonglong; Cao, Ruiyuan; Yin, Yuanyuan; Chen, Jing; Zhao, Liang; Zhou, Yu; Zhong, Wu; Liu, Hong; Luo, Xiaomin; Chen, Lili; Shen, Xu

doi:10.1016/j.ejmech.2016.10.019

Cited by 25 publications

(17 citation statements)

References 41 publications

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“…However, many rupintrivir derivatives are currently under development [26][27][28]. Furthermore, non-peptidomimetic small molecule inhibitors are developed to circumvent difficulties with bioavailability [29], but they have yet to be evaluated in clinical trials.…”

Section: Protease Inhibitorsmentioning

confidence: 99%

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Bauer

Lyoo

Schaar

et al. 2017

Current Opinion in Virology

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Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.

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Section: Protease Inhibitorsmentioning

confidence: 99%

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Bauer

Lyoo

Schaar

et al. 2017

Current Opinion in Virology

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“…Besides, DC07090 has a very low cytotoxicity rate (CC 50 > 200 µM) which makes it an attractive compound for further drug development [43].…”

Section: Non-peptidyl Compound: Dc07090mentioning

confidence: 99%

Recent advances of enterovirus 71 $$3{\rm C}^{{\rm pro}}$$ targeting Inhibitors

Diarimalala¹,

Hu²,

Hu³

2020

Virol J

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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. $$3{\rm C}^{{\rm pro}}$$ 3 C pro is a protease which plays important functions in EV71 infection. To date, a lot of $$3{\rm C}^{{\rm pro}}$$ 3 C 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, $$3{\rm C}^{{\rm pro}}$$ 3 C pro functions and $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors recently screened. It permits to well understand all mechanisms about $$3{\rm C}^{{\rm pro}}$$ 3 C pro and consequently allow further development of drugs targeting $$3{\rm C}^{{\rm pro}}$$ 3 C pro . Thus, this review is helpful for screening of more new $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors or for designing analogues of well known $$3{\rm C}^{{\rm pro}}$$ 3 C pro inhibitors in order to improve its antiviral activity.

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“…Modifying the labile cyanohydrin moiety led to the discovery of the 4-iminooxazolidin-2-one-based inhibitors 4e and 4 g with potent inhibitory activity and significantly improved stability [36]. One small-molecule inhibitor, DC07090, inhibited EV-A71 replication with an EC 50 value of 22.09 ± 1.07 μM by targeting 3C protease [37]. Luteoloside is a member of the flavonoids family that exhibits several bioactivities, including anti-microbial and anti-cancer activities, and was also shown to act as a 3C protease inhibitor of EV-A71 in vitro [38].…”

Section: Inhibitors Of the Ev-a71 Life Cyclementioning

confidence: 99%

Antivirals and vaccines for Enterovirus A71

2019

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Enterovirus A71 (EV-A71) is an important emerging virus posing a threat to children under five years old. EV-A71 infection in infants or young children can cause hand-foot-and-mouth disease, herpangina, or severe neurological complications. However, there are still no effective antivirals for treatment of these infections. In this review, we summarize the antiviral compounds developed to date based on various targets of the EV-A71 life cycle. Moreover, development of a vaccine would be the most effective approach to prevent EV-A71 infection. Therefore, we also summarize the development and clinical progress of various candidate EV-A71 vaccines, including inactivated whole virus, recombinant VP1 protein, synthetic peptides, viral-like particles, and live attenuated vaccines.

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Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening

Cited by 25 publications

References 41 publications

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Recent advances of enterovirus 71 $$3{\rm C}^{{\rm pro}}$$ targeting Inhibitors

Antivirals and vaccines for Enterovirus A71

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