Penner Robert C
Institut des Hautes Études Scientifiques, Bures-sur-Yvette, France.
Mathematics Department, University of California at Los Angeles, Los Angeles, California, USA.
J Comput Biol. 2020 Nov;27(11):1622-1630. doi: 10.1089/cmb.2020.0193. Epub 2020 May 13.
Methods previously developed by the author are applied to uncover several sites of interest in the spike glycoproteins of all known human coronaviruses (hCoVs), including SARS-CoV-2 that causes COVID-19. The sites comprise three-dimensional neighborhoods of peptides characterized by four key properties: (1) they pinpoint regions of high free energy in the backbone whose obstruction might interrupt function; (2) by their very definition, they occur rarely in the universe of all gene-encoded proteins that could obviate host response to compounds designed for their interference; (3) they are common to all known hCoV spikes, possibly retaining activity in light of inevitable viral mutation; and (4) they are exposed in the molecular surface of the glycoprotein. These peptides in SARS-CoV-2 are given by the triples of residues (131, 117, 134), (203, 227, 228), and (1058, 730, 731) in its spike.
作者先前开发的方法被用于揭示所有已知人类冠状病毒（hCoV）刺突糖蛋白中的几个感兴趣位点，包括导致COVID-19的SARS-CoV-2。这些位点包括具有四个关键特性的肽的三维邻域：（1）它们确定了主链中高自由能区域，其受阻可能会中断功能；（2）根据其定义，它们在所有基因编码蛋白的宇宙中很少出现，这可能会消除宿主对为干扰它们而设计的化合物的反应；（3）它们在所有已知的hCoV刺突中都很常见，鉴于不可避免的病毒突变可能仍保持活性；（4）它们暴露在糖蛋白的分子表面。SARS-CoV-2中的这些肽由其刺突中残基的三元组（131、117、134）、（203、227、228）和（1058、730、731）给出。
