Close Genetic Relative of SARS-CoV-2 Found in Bats Offers More Evidence It Evolved Naturally

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Flying Greater Horseshoe Bat

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There is continuous dispute amongst policymakers and the public about where SARS-CoV-2, the infection that triggers COVID-19, originated from. While scientists think about bats the most likely natural hosts for SARS-CoV-2, the origins of the infection are still uncertain.

Recently, in the journal Current Biology, scientists explain a just recently determined bat coronavirus that is SARS-CoV-2’s closest relative in some areas of the genome and which consists of insertions of amino acids at the junction of the S1 and S2 subunits of the infection’s spike protein in a way comparable to SAR-CoV-2. While it’s not a direct evolutionary precursor of SARS-CoV-2, this brand-new infection, RmYN02, recommends that these kinds of relatively uncommon insertion occasions can take place naturally in coronavirus advancement, the scientists state.

“Since the discovery of SARS-CoV-2 there have been a number of unfounded suggestions that the virus has a laboratory origin,” states senior author Weifeng Shi, director and teacher at the Institute of Pathogen Biology at Shandong First Medical University in China. “In particular, it has been proposed the S1/S2 insertion is highly unusual and perhaps indicative of laboratory manipulation. Our paper shows very clearly that these events occur naturally in wildlife. This provides strong evidence against SARS-CoV-2 being a laboratory escape.”

The scientists determined RmYN02 from an analysis of 227 bat samples gathered in Yunnan province, China, in between May and October of 2019. “Since the discovery that bats were the tank of SARS coronavirus in 2005, there has actually been fantastic interest in bats as tank types for transmittable illness, especially as they bring an extremely high variety of RNA infections, consisting of coronaviruses,” Shi states. RNA from the samples was sent out for metagenomic next-generation sequencing in early January 2020, not long after the discovery of SARS-CoV-2.

Across the entire genome, the closest relative to SARS-CoV-2 is another infection, called RaTG13, which was formerly determined from bats in Yunnan province. But RmYN02, the infection recently found here, is much more carefully associated to SARS-CoV-2 in some parts of the genome, consisting of in the longest encoding area of the genome called 1ab, where they share 97.2% of their RNA. The scientists keep in mind that RmYN02 does not carefully look like SAR-CoV-2 in the area of the genome that encodes the essential receptor binding domain that binds to the human ACE2 receptor that SARS-CoV-2 utilizes to contaminate host cells. This suggests it’s not most likely to contaminate human cells.

The essential resemblance in between SARS-CoV-2 and RmYN02, is the finding that RmYN02 likewise consists of amino acid insertions at the point where the 2 subunits of its spike protein fulfill. SARS-CoV-2 is identified by a four-amino-acid insertion at the junction of S1 and S2; this insertion is distinct to the infection and has actually existed in all SARS-CoV-2 sequenced up until now. The insertions in RmYN02 are not the like those in SARS-CoV-2, which suggests that they happened through independent insertion occasions. But a comparable insertion occasion taking place in an infection determined in bats highly recommends that these type of insertions are of natural origin. “Our findings suggest that these insertion events that initially appeared to be very unusual can, in fact, occur naturally in animal betacoronaviruses,” Shi states.

“Our work sheds more light on the evolutionary ancestry of SARS-CoV-2,” he includes. “Neither RaTG13 nor RmYN02 is the direct ancestor of SARS-CoV-2, because there is still an evolutionary gap between these viruses. But our study strongly suggests that sampling of more wildlife species will reveal viruses that are even more closely related to SARS-CoV-2 and perhaps even its direct ancestors, which will tell us a great deal about how this virus emerged in humans.”

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Reference: “A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2Cleavage Site of the Spike Protein” by Hong Zhou, Xing Chen, Tao Hu, Juan Li, Hao Song, Yanran Liu, Peihan Wang, Di Liu, Jing Yang, Edward C. Holmes, Alice C. Hughes, Yuhai Bi and Weifeng Shi, 10 May 2020, Current Biology.
DOI: 10.1016/j.cub.2020.05.023

This work was supported by the Academic Promotion Programme of Shandong First Medical University, the Strategic Priority Research Programme of the Chinese Academy of Sciences, the Chinese National Natural Science Foundation, the National Major Project for Control and Prevention of Infectious Disease in China, the High-End Foreign Experts Program of Yunnan Province, the Taishan Scholars Programme of Shandong Province, the NSFC Outstanding Young Scholars, Youth Innovation Promotion Association of CAS, and an ARC Australian Laureate Fellowship.

Current Biology, Zhou et al.: “A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein”



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