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-Structure paper
| タイトル | A novel druggable interprotomer pocket in the capsid of rhino- and enteroviruses. |
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| ジャーナル・号・ページ | PLoS Biol, Vol. 17, Issue 6, Page e3000281, Year 2019 |
| 掲載日 | 2019年6月11日 |
著者 | Rana Abdelnabi / James A Geraets / Yipeng Ma / Carmen Mirabelli / Justin W Flatt / Aušra Domanska / Leen Delang / Dirk Jochmans / Timiri Ajay Kumar / Venkatesan Jayaprakash / Barij Nayan Sinha / Pieter Leyssen / Sarah J Butcher / Johan Neyts / ![]() |
| PubMed 要旨 | Rhino- and enteroviruses are important human pathogens, against which no antivirals are available. The best-studied inhibitors are "capsid binders" that fit in a hydrophobic pocket of the viral ...Rhino- and enteroviruses are important human pathogens, against which no antivirals are available. The best-studied inhibitors are "capsid binders" that fit in a hydrophobic pocket of the viral capsid. Employing a new class of entero-/rhinovirus inhibitors and by means of cryo-electron microscopy (EM), followed by resistance selection and reverse genetics, we discovered a hitherto unknown druggable pocket that is formed by viral proteins VP1 and VP3 and that is conserved across entero-/rhinovirus species. We propose that these inhibitors stabilize a key region of the virion, thereby preventing the conformational expansion needed for viral RNA release. A medicinal chemistry effort resulted in the identification of analogues targeting this pocket with broad-spectrum activity against Coxsackieviruses B (CVBs) and compounds with activity against enteroviruses (EV) of groups C and D, and even rhinoviruses (RV). Our findings provide novel insights in the biology of the entry of entero-/rhinoviruses and open new avenues for the design of broad-spectrum antivirals against these pathogens. |
リンク | PLoS Biol / PubMed:31185007 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 4.0 Å |
| 構造データ | |
| 化合物 | ![]() ChemComp-FHK: |
| 由来 |
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キーワード | VIRUS / Inhibitor / complex |
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coxsackievirus b3 (strain nancy) (コクサッキーウイルス)
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