Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019

Matthew C. Wong; Sara J. Javornik Cregeen; Nadim J. Ajami; Joseph F. Petrosino

Amino acid alignment between pangolin coronavirus and nCoV-2019 at the S1-NTD subdomain results in low sequence similarity. However, increased similarity is observed from the RBD through the S2 domain ( Figure 1A-B) . This suggests a possible recombination event between a bat coronavirus and the pangolin coronavirus at the S1-NTD and RBD junction. While there is high conservation at the amino-acid level between the pangolin coronavirus and nCoV-2019, this is not reflected in the nucleotide identity, suggesting that the proposed recombination event occurred in the more distant past, allowing subsequent time for genetic drift. One such mutation could be the insertion of the amino acid residues PRRA near the S1/S2 junction which induces a furin cleavage motif. The secondary requirement for entry into the host cell is proteolytic cleavage of the S1/S2 domains in order to mediate membrane fusion post ACE2 binding 4 , and introduction of the furin cleavage motif may be another factor in nCoV-2019 being able to replicate in humans ( Figure 2 ). author/funder. All rights reserved. No reuse allowed without permission.