Abstract |
Human enterovirus A71 (EV-A71) is a major etiological agent of hand-foot-and-mouth disease (HFMD) and there is presently no internationally approved antiviral against EV-A71. In this study, it is disclosed that 14S-(2'-chloro-4'-nitrophenoxy)-8R/S,17-epoxy andrographolide (2) was discovered to be an effective inhibitor against EV-A71 infection showing significant reduction of viral titre. In addition to EV-A71, compound 2 exerts broad-spectrum antiviral effects against other enteroviruses. It is revealed that compound 2 inhibits the post-entry stages of EV-A71 viral replication cycle and significantly reduces viral protein expression of structural proteins such as VP0 and VP2 via inhibiting EV-A71 RNA replication. Moreover, the inhibitory property of compound 2 is specific to viral RNA replication. Furthermore, compound 2 is more likely to target a host factor in EV-A71 RNA replication. As a result, introduction of epoxide at positions 8 and 17 of andrographolide is effective for anti-EV-A71 infection and is a potential anti-EV-A71 strategy. Further work to discover more potent andrographolide derivatives and elucidate comprehensive SAR is under way.
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Authors | Kun Dai, Jie Kai Tan, Weiyi Qian, Regina Ching Hua Lee, Justin Jang Hann Chu, Guo-Chun Zhou |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 194
Pg. 114820
(12 2021)
ISSN: 1873-2968 [Electronic] England |
PMID | 34748818
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
Chemical References |
- Diterpenes
- andrographolide
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Topics |
- Animals
- Cell Survival
(drug effects, physiology)
- Chlorocebus aethiops
- Diterpenes
(chemistry, pharmacology, therapeutic use)
- Dose-Response Relationship, Drug
- Drug Discovery
(methods)
- Enterovirus A, Human
(drug effects, physiology)
- Enterovirus Infections
(drug therapy, metabolism)
- Humans
- Vero Cells
- Virus Replication
(drug effects, physiology)
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