Patient-derived mutations impact pathogenicity of SARS-CoV-2

Hangping Yao; Xiangyun Lu; Qiong Chen; Kaijin Xu; Yu Chen; Linfang Cheng; Fumin Liu; Zhigang Wu; Haibo Wu; Changzhong Jin; Min Zheng; Nanping Wu; Chao Jiang; Lanjuan Li

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.14.20060160 doi: medRxiv preprint 23 removed. Although the Vero-E6 cell line was not derived from human, the ACE2 protein 316 of the Vero-E6 cell line is highly similar to that of Human (Fig. S6 ) and we provided 317 direct evidence that the SARS-CoV-2 can infect the cell line (Fig. 2B) . 318 Several findings stand out in our study: 1. A diverse collection of mutations was 319 identified in the 11 viral isolates, including two sets of founding mutations for two major 320 clusters of viruses currently infecting the world population. In addition, 19 of the 31 321 identified mutations are novel, despite the relatively early sampling dates, indicating that 322 the true diversity of the viral strains is still largely underappreciated; 2. remarkably, the 323 T22303G and A22301C mutations result in the same S247R mutation in the S protein 324 ( Fig. 1 and S1 ), mapping to the existing structure revealed that this residue is located in a 325 flexible loop region within the N-terminal domain of the S1 subunit of S protein, 326 although the exact position of S247 could not be determined (Fig. S7, red arch) . While 327 the N-terminal domain is not directly involved with binding to ACE2 (Walls et al., 2020) 328 we note that this domain is positioned right next to the C-terminal domain, which binds to 329 ACE2. Interestingly, the T22303G mutation was observed in 5 viral isolates, albeit in 330 different proportions, indicating that this specific mutation was already present in the 331 early days of pandemic, and probably in a significant number of people of Wuhan, 332 All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.