Coronaviruses Related to SARS-CoV-2 Discovered in Japan and Cambodia

The viruses, both isolated from bats stored in a laboratory’s freezers, are the first relatives of SARS-CoV-2 to be found outside of China. Research on them sheds light on the origin of the pandemic coronavirus.   Coronaviruses constitute a large family of viruses that can infect humans—as the current pandemic reminds us—as well as animals. The phylogenetic tree linking this family is very broad, and from one end to the other, the viruses are more or less similar. SARS-CoV-2 is probably not an entirely new coronavirus that appeared suddenly. Viruses in this group have likely existed since well before its discovery in 2019. It was therefore with great enthusiasm and curiosity that researchers identified the first close relatives of SARS-CoV-2 discovered outside of China. The first was found in two rhinolophus bats (or horseshoe bats) captured in 2010 in Cambodia, and the second in rhinolophus bats in Japan in 2013. Until then, only a few coronaviruses discovered in China were closely related to SARS-CoV-2. Among these was its closest known relative, RaTG13, discovered in horseshoe bats in China’s Yunnan province in 2013. There are also several coronaviruses—identified in other horseshoe bats and in pangolins captured between 2015 and 2019 in China—that scientists now consider to be closely related to SARS-CoV-2. While the origin of the pandemic coronavirus remains a mystery, these discoveries could shed light on the “past” of SARS-CoV-2. For now, the leads being pursued point toward horseshoe bats, but the question of transmission via an intermediate host remains unresolved. Preliminary sequencing of a short fragment of the new Cambodian virus, which is highly conserved among coronaviruses and is often used to quickly determine whether a virus is new or not, showed similarities to SARS-CoV-2 and RaTG13, suggesting that the three are closely related. In another analysis, the Cambodian team sequenced approximately 70% of the new virus’s genome using locally available genomics technology. However, its entire genome has not yet been fully sequenced, nor has its discovery been published, which further limits the ability to determine the impact of this finding on the current pandemic. The new virus would need to be at least 99% similar to SARS-CoV-2 to be considered a direct ancestor of the current pandemic virus. The genomes of RaTG13 and SARS-CoV-2 differ by only 4%, but this divergence represents between 40 and 70 years of evolution. If the virus turns out to be very closely related to—or even an ancestor of—the pandemic coronavirus, it could provide crucial information about the origin of the pandemic and the mechanisms that allowed SARS-CoV-2 to jump from bats to humans. To gain such insights, the Cambodian “cousin” would need to share more than 97% of its genome with SARS-CoV-2, which has not yet been confirmed. It is possible that the new virus is more distantly related, but in that case, studying it will help scientists learn more about the diversity of this viral family. This was the case with the Japanese coronavirus, nicknamed Rc-o319. It shares 81% of its genome with SARS-CoV-2, making it too distantly related to provide insight into the origin of the pandemic. In fact, the virus cannot bind to the ACE2 receptor used by SARS-CoV-2 to enter human cells, suggesting that it would not be able to easily infect humans. But regardless of the findings regarding the Cambodian virus, both discoveries are significant. They confirm that viruses closely related to SARS-CoV-2 are relatively common among rhinolophus bats, even outside of China. Other close relatives of the virus, as yet unknown, could still be lurking in laboratory freezers. The hunt for the virus, therefore, remains open.