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https://doi.org/10.1016/j.bcp.2021.114820
Title: | Discovery of 14S-(2’-chloro-4’-nitrophenoxy)-8R/S,17-epoxy andrographolide as EV-A71 infection inhibitor | Authors: | Dai, K Tan, JK Qian, W Lee, RCH Hann Chu, JJ Zhou, GC |
Keywords: | Andrographolide Broad-spectrum anti-enterovirus agent Epoxide Human enterovirus A71 Targeting host factor Viral RNA replication Animals Cell Survival Chlorocebus aethiops Diterpenes Dose-Response Relationship, Drug Drug Discovery Enterovirus A, Human Enterovirus Infections Humans Vero Cells Virus Replication |
Issue Date: | 1-Dec-2021 | Publisher: | Elsevier BV | Citation: | Dai, K, Tan, JK, Qian, W, Lee, RCH, Hann Chu, JJ, Zhou, GC (2021-12-01). Discovery of 14S-(2’-chloro-4’-nitrophenoxy)-8R/S,17-epoxy andrographolide as EV-A71 infection inhibitor. Biochemical Pharmacology 194 : 114820-. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bcp.2021.114820 | 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. | Source Title: | Biochemical Pharmacology | URI: | https://scholarbank.nus.edu.sg/handle/10635/235429 | ISSN: | 0006-2952 1873-2968 |
DOI: | 10.1016/j.bcp.2021.114820 |
Appears in Collections: | Elements Staff Publications |
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1-s2.0-S0006295221004366-main.pdf | Published version | 3.61 MB | Adobe PDF | CLOSED | Published | |
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