Strong evolutionary convergence of receptor-binding protein spike between COVID-19 and SARS-related coronaviruses

Yonghua Wu

The 2019 novel coronavirus (2019-nCoV, also called severe acute respiratory syndrome (SARS)-CoV-2) has caused the current outbreak of coronavirus disease (COVID-19), which has emerged as a serious public health concern. The clinical and pathological features caused by 2019-nCoV resemble those seen in SARS 1-3 , which is caused by SARS coronavirus (SARS-CoV). Both 2019-nCoV and SARS-CoV have been determined to be of bat origin, with possible intermediate hosts prior to infecting humans 4,5 . Phylogenetic studies have shown that 2019-nCoV and SARS-CoV belong to the subgenus Sarbecovirus, but they are distantly related 5-8 , with a sequence identity of 79.6% at the whole-genome level 5 . One recent study showed that 2019-nCoV is more similar to a bat coronavirus (RaTG13), with a sequence identity of 96.2% at the whole-genome level, than many other coronaviruses from different hosts, suggesting a phylogenetic affinity of 2019-nCoV to bat coronavirus compared with SARS-CoV 5 . Despite their relatively distant phylogenetic relationships, 2019-nCoV and SARS-CoV are both known to be capable of infecting humans using the same cell receptor, angiotensin-converting enzyme 2 (ACE2) 5,6,9,10 , and their protein structures of receptor-binding protein spike (S) are found to be highly similar to each other 10,11 , suggesting their phenotypic convergence. The spike protein is responsible for receptor binding and membrane fusion, and it is important for host tropism and transmission capacity 6 . The spike protein of coronaviruses comprises two subunits, S1 and S2. The S1 subunit contains a receptorbinding domain (RBD), which harbors a receptor-binding motif (RBM) to make complete contact with the receptor (i.e., ACE2) 12,13 .