A furin cleavage site was discovered in the S protein of the 2019 novel coronavirus

ABSTRACT

The 2019 novel Coronavirus (2019-nCoV) has caused the pneumonia outbreak in Wuhan (a city of China). In our previous study, the analytical results showed that both 2019-nCoV and SARS coronavirus belong to Betacoronavirus subgroup B (BB coronavirus), but have large differences, which are consistent with the differences in the clinical symptoms of two related diseases. The most important finding was that the alternative translation of Nankai CDS could produce more than 17 putative proteins, which may be responsible for the host adaption. The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of BB coronavirus. The present study for the first time (on January 21st, 2020) reported a very important mutation in the Spike (S) proteins of Betacoronavirus. By this mutation, 2019-nCoV acquired a cleavage site for furin enzyme in its S protein, which is not present in the S proteins of most other Betacoronavirus (e.g. SARS coronavirus). This cleavage site may increase the efficiency of virus infection into cells, making 2019-nCoV has significantly stronger transmissibility than SARS coronavirus. The infection mechanism of 2019-nCoV may be changed to being more similar to those of MHV, HIV, Ebola virus (EBoV) and some avian influenza viruses, other than those of most other Betacoronavirus (e. g. SARS coronavirus). In addition, we unexpectedly found that some avian influenza viruses acquired a cleavage site for furin enzyme by the similar mutation as 2019-nCoV. Therefore, the natural mutation can result in a short insertion to form a cleavage site for furin enzyme. The cleavage site for furin enzyme in 2019-nCoV contains the "CGGCGG" sequence encoding two arginine (R) residues. "CGG", however, is a rare codon for human. So we concluded that these two codons were present in the 2019-nCoV -like Betacoronavirus before they transmitted into human and the intermediate host (s) are mammals with a high relative frequency of "CGG" usage. We provide a relative frequency table of " CGG" usage in mammals to help identify the intermediate hosts of 2019-nCoV. Future studies of this mutation will help to reveal the stronger transmissibility of 2019-nCoV and lay foundations for vaccine development and drug design of, but not limited to 2019-nCoV.