Tsang S K, Danthi P, Chow M, Hogle J M
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA, 02138, USA.
J Mol Biol. 2000 Feb 18;296(2):335-40. doi: 10.1006/jmbi.1999.3483.
When poliovirus attaches to its receptor or is heated in hypotonic buffers, the virion undergoes an irreversible conformational transition from the native 160 S (or N) particle to the 135 S (or A) particle, which is believed to mediate cell entry. The first-order rate constants for the thermally induced transition have been measured as a function of temperature for virus alone and for complexes of the virus with capsid-binding drugs that inhibit the receptor and thermally mediated conversion. Although the drugs have minimum inhibitory concentrations (MIC) that differ by almost three orders of magnitude, the activation energies for the N to A transition for the drug complexes (145 kcal/mol) were indistinguishable from each other or from that of the virus alone. We conclude that the antiviral activity of these drugs derives from a novel mechanism in which drug-binding stabilizes the virions through entropic effects.
当脊髓灰质炎病毒附着于其受体或在低渗缓冲液中加热时，病毒粒子会经历从天然的160S（或N）颗粒到135S（或A）颗粒的不可逆构象转变，据信后者介导细胞进入。已经测量了单独病毒以及病毒与抑制受体和热介导转化的衣壳结合药物复合物的热诱导转变的一级速率常数与温度的函数关系。尽管这些药物的最低抑菌浓度（MIC）相差近三个数量级，但药物复合物从N到A转变的活化能（145千卡/摩尔）彼此之间以及与单独病毒的活化能没有区别。我们得出结论，这些药物的抗病毒活性源自一种新机制，即药物结合通过熵效应稳定病毒粒子。
