Orally active fusion inhibitor of respiratory syncytial virus

被引：112

作者：

Cianci, C ^{[1
]}

Yu, KL ^{[1
]}

Combrink, K ^{[1
]}

Sin, N ^{[1
]}

Pearce, B ^{[1
]}

Wang, A ^{[1
]}

Civiello, R ^{[1
]}

Voss, S ^{[1
]}

Luo, GX ^{[1
]}

Kadow, K ^{[1
]}

Genovesi, EV ^{[1
]}

Venables, B ^{[1
]}

Gulgeze, H ^{[1
]}

Trehan, A ^{[1
]}

James, J ^{[1
]}

Lamb, L ^{[1
]}

Medina, I ^{[1
]}

Roach, J ^{[1
]}

Yang, Z ^{[1
]}

Zadjura, L ^{[1
]}

Colonno, R ^{[1
]}

Clark, J ^{[1
]}

Meanwell, N ^{[1
]}

Krystal, M ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2004年 / 48卷 / 02期

关键词：

D O I：

10.1128/AAC.48.2.413-422.2004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

BMS-433771 was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. It exhibited excellent potency against multiple laboratory and clinical isolates of both group A and B viruses, with an average 50% effective concentration of 20 nM. Mechanism-of-action studies demonstrated that BMS-433771 inhibits the fusion of lipid membranes during both the early virus entry stage and late-stage syncytium formation. After isolation of resistant viruses, resistance was mapped to a series of single amino acid mutations in the F1 subunit of the fusion protein. Upon oral administration, BMS-433771 was able to reduce viral titers in the lungs of mice infected with RSV. This new class of orally active RSV fusion inhibitors offers potential for clinical development.

引用

页码：413 / 422

页数：10

共 67 条

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