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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.02.974139 doi: bioRxiv preprint 7 alignment). The amino acid deletions in RmYN02 RBD made two loops near the receptor 128 binding site that are shorter than those in HCoV-19 RBD (Fig. 2a and 2f) . Importantly, the 129 conserved disulfide bond in the external subdomain of SARS-CoV (PDB: 2DD8) 12 , HCoV-19 130 (PDB: 6LZG), RaTG13 (Fig. 2b) , pangolin/MP789/2019 (Fig. 2c) and pangolin/GX/P5L/2017 131 (Fig. 2d) was missing in RmYN02 (Fig. 2f) . We speculate that these deletions may cause 132 conformational variations and consequently reduce the binding of RmYN02 RBD with ACE2 133 or even cause non-binding. It is possible that the bat SARS-related CoVs with loop deletions, 134 including RmYN02, ZXC21 and ZC45, use a currently unknown receptor. In contrast, RaTG13 135 . 149 author/funder. All rights reserved. No reuse allowed without permission.