The Enterovirus 3C Protease Inhibitor SG85 Efficiently Blocks Rhinovirus Replication and Is Not Cross-Resistant with Rupintrivir

被引：19

作者：

Lacroix, Celine ^{[1
]}

George, Shyla ^{[2
]}

Leyssen, Pieter ^{[1
]}

Hilgenfeld, Rolf ^{[2
,3
]}

Neyts, Johan ^{[1
]}

机构：

[1] Katholieke Univ Leuven, Rena Inst Med Res, Virol Lab, Leuven, Belgium

[2] Med Univ Lubeck, Inst Biochem, Ctr Struct & Cell Biol Med, D-23538 Lubeck, Germany

[3] Med Univ Lubeck, German Ctr Infect Res DZIF, Hamburg Lubeck Borstel Site, D-23538 Lubeck, Germany

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2015年 / 59卷 / 09期

关键词：

STRUCTURE-BASED DESIGN; VITRO ANTIVIRAL ACTIVITY; BIOLOGICAL EVALUATION; RNA-BINDING; INFECTION;

D O I：

10.1128/AAC.00534-15

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The novel enterovirus protease inhibitor (PI) SG85 effectively inhibits the in vitro replication of 14 rhinoviruses representative of species A and B (median 50% effective concentration, 0.04 mu M). A low-level SG85-resistant variant was selected that carried amino acid substitutions S127G and T143A in the 3C protease. Both substitutions are required for low-level resistance to SG85, as demonstrated by reverse genetics. Interestingly, there is no cross-resistance to SG85 and rupintrivir (another PI); a structural explanation is provided for this observation.

引用

页码：5814 / 5818

页数：5

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