A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19

Hong Zhou; Xing Chen; Tao Hu; Juan Li; Hao Song; Yanran Liu; Peihan Wang; Di Liu; Jing Yang; Edward C. Holmes; Alice C. Hughes; Yuhai Bi; Weifeng Shi

HCoV-19 has increased sharply since January 21, 2020, and as of March 2rd, 2020, more than 59 80,000 confirmed HCoV-19 cases have been reported, with >11,000 severe cases and >2900 60 deaths in China. By the end of January confirmed HCoV-19 cases were present in all the 61 author/funder. All rights reserved. No reuse allowed without permission. and feces (n=78). All but three bats were sampled alive and subsequently released. Based on 89 the bat species primarily identified according to morphological criteria and confirmed 90 through DNA barcoding, the 224 tissues and 78 feces were merged into 38 and 18 pools, 91 respectively, with each pool including 1 to 11 samples of the same type (Extended Data Table 92 1). These pooled samples were then used for next generation sequencing (NGS). polymorphisms in the NGS data, although these did not include the S1/S2 cleavage site 104 (Extended Data Figure 3) . Only a few reads in the remaining 55 pools could be mapped to 105 author/funder. All rights reserved. No reuse allowed without permission. (Fig. 1a) . RmYN02 and HCoV-19 were extremely similar (>96% sequence identity) in 112 most genomic regions (e.g. 1ab, 3a, E, 6, 7a, N and 10) (Fig. 1a) . In particular, RmYN02 was 113 97.2% identical to HCoV-19 in the longest encoding gene region, 1ab (n=21285). However, 114