肠道病毒(EV和RV)在世界范围内普遍存在,并在人类中引起各种疾病,其中VP1口袋是抗病毒药物的目标,用脂质分子作为口袋因子来稳定病毒体。然而,电动汽车中VP1口袋的结构表征较差。这里,我们比较了已发布的电动汽车和房车的衣壳晶体,并提出了VP1口袋的结构框架:框架1-4,它位于CD环路,GH循环,和C端,呈现或不呈现向外开放的外观。非外向病毒株-CVB3,Echo11,RV-A81和RV-B70-更热稳定,基因组释放的断点温度(B.T.)为51〜62°C,比其外部温度41〜47°C高4〜10°C,和感染性保存在50°C下处理3分钟。它的向外开放和非向外开放与基因组释放(r=-0.90;p=0.0004)和感染性(r=-0.82,p=0.0039)的B.T.显着相关。帧1、2和4的能量,包括范德华吸引和排斥相互作用以及氢键,显示与B.T.的显着相关性(r=-0.67、0.75和-0.8;p分别为0.034、0.013和0.006)。VP1口袋的这些特征可能是病毒体热稳定性的预测因子,并有助于疫苗或抗病毒药物的开发。
Enteroviruses (EVs and RVs) are prevalent worldwide and cause various diseases in humans, of which the VP1-pocket is a target of antivirals, with a lipid molecule as a pocket factor to stabilize the virion. However, the characterization of the structure of the VP1-pocket in EVs is poor. Here, we compared the published capsid crystals of EVs and RVs and proposed a structural framework for the VP1-pocket: Frame 1-4, which is located at the CD loop, GH loop, and C-terminus, presenting with an outward opening appearance or not. The non-outward viral strains-CVB3, Echo 11, RV-A81, and RV-B70-are more thermally stable, with a breakpoint temperature (B.T.) of 51~62 °C for genome releasing, which is 4~10 °C higher than its outward temperature of 41~47 °C, and infectivity preservation when treated at 50 °C for 3 min. Its outward versus non-outward opening is correlated significantly with the B.T. for genome release (r = -0.90; p = 0.0004) and infectivity (r = -0.82, p = 0.0039). The energy of Frames 1, 2, and 4, including Van der Waals attractive and repulsive interactions and hydrogen bonds, showed significant correlations with the B.T. (r = -0.67, 0.75, and -0.8; p = 0.034, 0.013, and 0.006, respectively). These characters of the VP1-pocket could be predictors for virion
thermostability and aid in the development of vaccines or antivirals.