| Virus Name | Enterovirus 71 |
| Virus Short Name | EV-71 |
| Order | Picornavirales |
| Virus Family | Picornaviridae |
| Virus Subfamily | N.A. |
| Genus | Enterovirus |
| Species | Enterovirus A |
| Host | Human, mammals |
| Cell Tropism | The gastrointestinal trac |
| Associated Disease | Hand, foot and mouth disease, meningitis |
| Mode of Transmission | Either fecal-oral or respiratory |
| VIPR DB link | https://www.viprbrc.org/brc/home.spg?decorator=picorna |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/234/picornaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Picornaviridae |
| Paper Title | Antiviral screen identifies EV71 inhibitors and reveals camptothecin-target, DNA topoisomerase 1 as a novel EV71 host factor |
| Author's Name | Kan Xing Wu, Justin Jang-Hann Chu |
| Journal Name | Antiviral Research |
| Pubmed ID | 28427827 |
| Abstract | Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth disease (HFMD) associated with severe neurological disease. EV71s pathogenesis remains poorly understood and the lack of approved antiviral has led to its emergence as a clinically important neurotropic virus. The goals of this study were to: (i) identify novel anti-EV71 compounds that may serve as lead molecules for therapeutics and (ii) investigate their targets in downstream studies. We screened a 502-compound library of highly purified natural products for anti-EV71 activities in a cell-based immunofluorescence assay that were then confirmed in viral plaque reduction assays. Along with known antivirals, novel inhibitors of EV71 were also identified. We selected camptothecin for downstream studies and found that it is a limited spectrum enterovirus inhibitor that inhibits coxsackievirus A16 but not ECHOvirus 7. Camptothecin, a DNAtopoisomerase 1 (TOP1) inhibitor, inhibits both viral RNA replication and translation based on luciferase replicon studies. Depletion of TOP1 using siRNA was then able to rescue EV71 infection from camptothecin inhibition. Interestingly, EV71 viral RNA replication and translation were also in TOP1 depleted cells. We found that nuclear TOP1 was relocalized to cytoplasmic replication vesicles during EV71 infection and localized with viral 3CD using confocal microscopy and proximity-ligation assays. Our findings reveal camptothecin to be a limited spectrum antiviral against enteroviruses that functions in a TOP1-dependent but cytotoxicity-independent manner. TOP1 is in turn needed for maximal EV71 viral RNA replication and viral protein synthesis. |
| Used Model | RD cells |
| DOI | 10.1016/j.antiviral.2017.04.008 |
