Badger J, Minor I, Kremer M J, Oliveira M A, Smith T J, Griffith J P, Guerin D M, Krishnaswamy S, Luo M, Rossmann M G
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
Proc Natl Acad Sci U S A. 1988 May;85(10):3304-8. doi: 10.1073/pnas.85.10.3304.
The binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. All of these bind into the same hydrophobic pocket within the viral protein VP1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. The compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. Although the antiviral potency of these compounds varies by 120-fold, they all induce the same conformational changes on the virion. The interactions of these compounds with the viral capsid are consistent with their observed antiviral activities against human rhinovirus 14 drug-resistant mutants and other rhinovirus serotypes. Crystallographic studies of one of these mutants confirm the partial sequencing data and support the finding that this is a single mutation that occurs within the binding pocket.
一系列八种抗病毒药物在进入宿主细胞后抑制小核糖核酸病毒脱壳，它们与14型人鼻病毒的结合已通过晶体学进行了表征。所有这些药物都结合到病毒蛋白VP1β桶状结构内的同一个疏水口袋中，尽管发现每种化合物在口袋中的方向和位置有所不同。这些化合物使蛋白质外壳的柔韧性降低，从而抑制解体。尽管这些化合物的抗病毒效力相差120倍，但它们都在病毒体上诱导相同的构象变化。这些化合物与病毒衣壳的相互作用与其对14型人鼻病毒耐药突变体和其他鼻病毒血清型的抗病毒活性一致。对其中一个突变体的晶体学研究证实了部分测序数据，并支持这是一个发生在结合口袋内的单一突变这一发现。
