Antiviral activities of peptide-based covalent inhibitors of the Enterovirus 71 3C protease

Hand, Foot and Mouth Disease is a highly contagious disease caused by a range of human enteroviruses. Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only va...

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Bibliographic Details
Published in:Scientific reports 2016-09, Vol.6 (1), p.33663, Article 33663
Main Authors: Tan, Yong Wah, Ang, Melgious Jin Yan, Lau, Qiu Ying, Poulsen, Anders, Ng, Fui Mee, Then, Siew Wen, Peng, Jianhe, Hill, Jeffrey, Hong, Wan Jin, Chia, Cheng San Brian, Chu, Justin Jang Hann
Format: Article
Language:English
Subjects:
3C Viral Proteases
631/154/309/2420
631/326/596/1296
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Cell Line
Cysteine Endopeptidases
Drug discovery
Drug Evaluation, Preclinical
Drug Synergism
Enterovirus - drug effects
Enterovirus A, Human - drug effects
Enterovirus A, Human - enzymology
Hand-foot-and-mouth disease
Humanities and Social Sciences
Humans
Infectious diseases
Inhibitory Concentration 50
multidisciplinary
Outbreaks
Peptides
Peptides - chemistry
Peptides - pharmacology
Protease inhibitors
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Proteinase inhibitors
Rhinovirus
Science
Viral Proteins - antagonists & inhibitors
Virus Replication - drug effects
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Summary:Hand, Foot and Mouth Disease is a highly contagious disease caused by a range of human enteroviruses. Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only vaccines are limited to circulation in China, presenting an unmet medical need that needs to be filled urgently. The human enterovirus 3 C protease has been deemed a plausible drug target due to its essential roles in viral replication. In this study, we designed and synthesized 10 analogues of the Rhinovirus 3 C protease inhibitor, Rupintrivir and tested their 3 C protease inhibitory activities followed by a cellular assay using human enterovirus 71 (EV71)-infected human RD cells. Our results revealed that a peptide-based compound containing a trifluoromethyl moiety to be the most potent analogue, with an EC 50 of 65 nM, suggesting its potential as a lead for antiviral drug discovery.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep33663