Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms

Jin, Xi; Lian, Jiang-Shan; Hu, Jian-Hua; Gao, Jianguo; Zheng, Lin; Zhang, Yi-Min; Hao, Shao-Rui; Jia, Hong-Yu; Cai, Huan; Zhang, Xiao-Li; Yu, Guo-Dong; Xu, Kai-Jin; Wang, Xiao-Yan; Gu, Jue-Qing; Zhang, Shan-Yan; Ye, Chan-Yuan; Jin, Ci-Liang; Lu, Ying-Feng; Yu, Xia; Yu, Xiao-Peng; Huang, Jian-Rong; Xu, Kang-Li; Ni, Qin; Yu, Cheng-Bo; Zhu, Biao; Li, Yong-Tao; Liu, Jun; Zhao, Hong; Zhang, Xuan; Yu, Liang; Guo, Yong-Zheng; Su, Jun-Wei; Tao, Jing-Jing; Lang, Guan-Jing; Wu, Xiao-Xin; Wu, Wen-Rui; Qv, Ting-Ting; Xiang, Dai-Rong; Yi, Ping; Shi, Ding; Chen, Yanfei; Ren, Yue; Qiu, Yun-Qing; Li, Lan-Juan; Sheng, Jifang; Yang, Yida

ZJ01 is a strain of SARS-CoV-2 with 29 381 bases. The results of the potential methylation sites of S protein sequences of SARS, Wuhan-Hu-1 and ZJ01 indicated that there were significant differences between SARS-CoV-2 and SARS. These coronaviruses can infect host cells through using the S protein to bind to the host cell surface receptor ACE2. During virus maturation, S proteins are glycosylated and divided into the parts S1 and S2. S1 is spherical and mainly involved in the recognition and binding of viruses to host cells. S2 is stalked and able to promote the fusion of the virus into host cells. The comparison results of three virus strains showed that ZJ01 and Wuhan-Hu-1 had one high-confidence site, two moderate-confidence sites and four low-confidence sites. SARS has three high-confidence sites, three moderate-confidence sites and five low-confidence sites. From the perspective of high-confidence sites (figure 1A, red arrow), the potential methylation points of SARS-CoV-2 (n=1) and SARS (n=3) are predominantly concentrated in the S1 and S2 segments of the S protein. The positions of two low-confidence sites and one medium-confidence site on S2 are relatively fixed among the three virus strains (blue arrow). These results suggest that the S proteins of the two viruses may have structural and functional differences due to m 6 A methylation during transcription and translation. Additionally, the results of gene sequence alignment ( figure 1B) showed that the variation in S protein sequences between ZJ01 and Wuhan-Hu-1 was subtle, and these variations were highly concentrated in the S2 segment. These variations resulted in five amino acid substitutions and two amino acid deletions. However, from the perspective of the simulated threedimensional protein structure, the effect of these variations on the overall S protein structure is relatively limited. The difference between SARS-CoV-2 and SARS is significant, especially at the specific recognition point position in segment S1 (figure 1C, red circle). On the one hand, this change may affect the viral binding force on host cells. On the other hand, the electrostatic changes between ZJ01 and Wuhan-Hu-1 are largely concentrated in the mutation zone of S2 (figure 1C, green ellipse), where the detailed mechanisms need further exploration.