School of Chemistry, University of Hyderabad, Hyderabad, India.
Proteins. 2021 May;89(5):569-576. doi: 10.1002/prot.26042. Epub 2021 Jan 17.
The human spike protein sequences from Asia, Africa, Europe, North America, South America, and Oceania were analyzed by comparing with the reference severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) protein sequence from Wuhan-Hu-1, China. Out of 10333 spike protein sequences analyzed, 8155 proteins comprised one or more mutations. A total of 9654 mutations were observed that correspond to 400 distinct mutation sites. The receptor binding domain (RBD) which is involved in the interactions with human angiotensin-converting enzyme-2 (ACE-2) receptor and causes infection leading to the COVID-19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE-2 receptor. The mutations observed in the spike proteins are discussed in the context of their distribution according to the geographical locations, mutation sites, mutation types, distribution of the number of mutations at the mutation sites and mutations at the glycosylation sites. The density of mutations in different regions of the spike protein sequence and location of the mutations in protein three-dimensional structure corresponding to the RBD are discussed. The mutations identified in the present work are important considerations for antibody, vaccine, and drug development.
对来自亚洲、非洲、欧洲、北美洲、南美洲和大洋洲的人类刺突蛋白序列与来自中国武汉的参考严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)蛋白序列进行了比较分析。在分析的 10333 个刺突蛋白序列中,有 8155 个蛋白包含一个或多个突变。共观察到 9654 个突变,对应 400 个不同的突变位点。参与与人类血管紧张素转换酶-2(ACE-2)受体相互作用并导致导致 COVID-19 疾病感染的受体结合域(RBD)包含 44 个突变,这些突变包括与 ACE-2 受体相互作用距离在 3.2Å 内的残基。根据地理位置、突变位点、突变类型、突变位点的突变数量分布以及糖基化位点的突变,对刺突蛋白中的突变进行了讨论。讨论了不同区域的刺突蛋白序列中的突变密度以及对应 RBD 的蛋白质三维结构中的突变位置。本研究中鉴定的突变是抗体、疫苗和药物开发的重要考虑因素。