All human viruses, including SARS-CoV-2, arose from spillovers from other animals. Results of a recent study of bat samples collected in a small region of Yunnan Province, China revealed additional close relatives of SARS-CoV-2 and SARS-CoV.
After the identification of SARS-CoV-2 in early 2020, wildlife sampling and retrospective genome sequencing revealed highly related viruses in animals. The virus RaTG13, from Rhinolophus affinis, shares the highest overall genome identity with SARS-CoV-2, 96.10%. The virus RmYN02 from the bat R. malayanus is the closest relative of SARS-CoV-2 in the ORF1ab open reading frame. Pangolin viruses from Guangdong have identical amino acids at six key residues in the receptor binding domain (RBD) needed for binding to human ACE2. A more distantly related coronavirus was isolated from a bat in Japan, and two viruses from Cambodia have 92.6% genome identity with SARS-CoV-2 and share five of six critical amino acids in the RBD. Finally a bat coronavirus from Thailand is closely related to RmYN02. These observations demonstrate that bats from a broad part of Asia harbor close relatives of SARS-CoV-2.
Fecal samples, oral swabs, and urine samples collected from mainly horseshoe bats in a small area of Yunnan Province between May 2019 – November 2020 were analyzed by RNA sequencing. The results revealed 9 novel betacoronaviruses and 17 alphacoronaviruses. Four of the betacoronaviruses were related to SARS-CoV-2 and three were related to SARS-CoV. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome with the exception of the spike gene. The other three SARS-CoV-2 related coronaviruses encode a spike gene that could weakly bind to the hACE2 receptor in vitro. Patches of high sequence identity in different regions of the genome illustrate the work of extensive recombination events.
While all the viruses identified in this study, as well as the previously discovered RmYN01 and RmYN02, were identified in a 1100 hectare part of Yunnan province, the results of ecological modeling show that many species of rhinolophid bats are present in much of Southeast Asia and southern China. Numerous other bat species and other wildlife inhabit this area, many of which can be infected by SARS-CoV-2. Hence much more wildlife sampling is needed to track potential spillovers of viruses into humans.
These findings also demonstrate that a very large part of Asia might harbor the direct ancestor of SARS-CoV-2. Remember that HIV/AIDS was first detected in Los Angeles in 1981 but the virus spilled over from a chimpanzee to a human in Africa in ~1920.