A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein

Zhao, Hong; Chen, Xing; Hu, T.; Li, Juan; Song, Hao; Liu, Yanran; Wang, Peihan; Liu, Di; Yang, Jing; Holmes, Edward C.; Hughes, Alice C.; Bi, Yang; Shi, Weifeng

doi:10.1016/j.cub.2020.09.030

Cited by 79 publications

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“…Indeed, a high diversity of coronavirus species have been found in Rhinolophus bats collected in several provinces of China 3 . To date, the closest relatives to SARS-CoV-2 were identified from bats sampled in the Yunnan province, southern China 1,4 . RaTG13 was isolated from a Rhinolophus affinis horseshoe bat in 2013, and RmYN02 from a Rhinolophus malayanus bats in 2019.…”

Section: Main Textmentioning

confidence: 99%

A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Hul

Delaune

Karlsson

et al. 2021

Preprint

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Knowledge of the origin and reservoir of the coronavirus responsible for the ongoing COVID-19 pandemic is still fragmentary. To date, the closest relatives to SARS-CoV-2 have been detected in Rhinolophus bats sampled in the Yunnan province, China. Here we describe the identification of SARS-CoV-2 related coronaviruses in two Rhinolophus shameli bats sampled in Cambodia in 2010. Metagenomic sequencing identified nearly identical viruses sharing 92.6% nucleotide identity with SARS-CoV-2. Most genomic regions are closely related to SARS-CoV-2, with the exception of a small region corresponding to the spike N terminal domain. The discovery of these viruses in a bat species not found in China indicates that SARS-CoV-2 related viruses have a much wider geographic distribution than previously understood, and suggests that Southeast Asia represents a key area to consider in the ongoing search for the origins of SARS-CoV-2, and in future surveillance for coronaviruses.

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Section: Main Textmentioning

confidence: 99%

A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Hul

Delaune

Karlsson

et al. 2021

Preprint

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“…This led to the concept that intermediate hosts are necessary for the transfer of CoVs to humans and perhaps for humanization, i.e., adaptation to human receptors (Wu et al, 2012;Li, 2013). Both SARS-CoV and SARS-CoV-2 are considered to have originated from Rhinolophus bats in China (Zhou P. et al, 2020;Zhou H. et al, 2020). Indeed, Sarbecoviruses, which are very similar to SARS-CoV-2, have been described in the Chinese horseshoe bats R. affinis (Zhou P. et al, 2020) and R. malayanus (Zhou H. et al, 2020).…”

Section: The Apparent "Multi-host Process" Of Coronavirus Emergencementioning

confidence: 99%

“…Molecular clock dating estimated that the divergence with the bat ancestor virus occurred in mid-2011 (Cotten et al, 2013). SARS-CoV-2, which emerged in 2019 in China shares 96% identity with BatCoV RaTG13 from Rhinolophus affinis (Zhou P. et al, 2020) and RmYN02 from Rhinolophus malayanus (Zhou H. et al, 2020). The only batCoV sequence ever found to be identical to that of human CoV is the RNA-dependent RNA polymerase (RdRp) gene of the MERS-CoV sequenced from T. perforatus in Saudi Arabia.…”

Section: Introduction Of Bats and Coronavirusesmentioning

confidence: 99%

Emergence of Bat-Related Betacoronaviruses: Hazard and Risks

et al. 2021

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The current Coronavirus Disease 2019 (COVID-19) pandemic, with more than 111 million reported cases and 2,500,000 deaths worldwide (mortality rate currently estimated at 2.2%), is a stark reminder that coronaviruses (CoV)-induced diseases remain a major threat to humanity. COVID-19 is only the latest case of betacoronavirus (β-CoV) epidemics/pandemics. In the last 20 years, two deadly CoV epidemics, Severe Acute Respiratory Syndrome (SARS; fatality rate 9.6%) and Middle East Respiratory Syndrome (MERS; fatality rate 34.7%), plus the emergence of HCoV-HKU1 which causes the winter common cold (fatality rate 0.5%), were already a source of public health concern. Betacoronaviruses can also be a threat for livestock, as evidenced by the Swine Acute Diarrhea Syndrome (SADS) epizootic in pigs. These repeated outbreaks of β-CoV-induced diseases raise the question of the dynamic of propagation of this group of viruses in wildlife and human ecosystems. SARS-CoV, SARS-CoV-2, and HCoV-HKU1 emerged in Asia, strongly suggesting the existence of a regional hot spot for emergence. However, there might be other regional hot spots, as seen with MERS-CoV, which emerged in the Arabian Peninsula. β-CoVs responsible for human respiratory infections are closely related to bat-borne viruses. Bats are present worldwide and their level of infection with CoVs is very high on all continents. However, there is as yet no evidence of direct bat-to-human coronavirus infection. Transmission of β-CoV to humans is considered to occur accidentally through contact with susceptible intermediate animal species. This zoonotic emergence is a complex process involving not only bats, wildlife and natural ecosystems, but also many anthropogenic and societal aspects. Here, we try to understand why only few hot spots of β-CoV emergence have been identified despite worldwide bats and bat-borne β-CoV distribution. In this work, we analyze and compare the natural and anthropogenic environments associated with the emergence of β-CoV and outline conserved features likely to create favorable conditions for a new epidemic. We suggest monitoring South and East Africa as well as South America as these regions bring together many of the conditions that could make them future hot spots.

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“…First, and most importantly, there is very little variability among the early emerging strains of the virus, challenging both molecular clock and outgroup rooting. Secondly, although the nearest outgroup sequence (RmYN02) is 97.2% identical to SARS-CoV-2 ( Zhou, Chen, et al 2020 ), the synonymous divergence is >11% revealing the presence of appreciable homoplasy, providing potential additional uncertainty for outgroup rooting. Thirdly, it is unclear if a molecular clock assumption is suitable during the early phases after zoonotic transfer where selection could possibly be quite strong.…”

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confidence: 99%

“…SARS-CoV-2, the virus causing COVID-19 or “severe acute respiratory syndrome,” has a single-stranded RNA genome 29,891 nucleotides in length ( Wu et al 2020 ; Zhou, Yang, et al 2020 ). The exact origin of the virus causing the human pandemic is unknown, but two coronaviruses isolated from bats—RaTG13 isolated from Rhinolophus affinis ( Zhou, Chen, et al 2020 ) and RmYN02 isolated from Rhinolophus malayanus ( Zhou, Yang, et al 2020 ), both from the Yunnan province of China—appear to be closely related. After accounting for recombination, the divergence time between these bat viruses and SARS-CoV-2 is estimated to be ∼52 years [95% CI (28, 75)] and 37 years [95% CI (18, 56)] ( Wang et al 2020 ), for RaTG13 and RmYN02, respectively, using a strict clock, only the most closely related sequences, and only synonymous mutations, or 51 years [95% HPD credible interval (40, 70)] for RaTG13 ( Boni et al 2020 ) using a relaxed clock and all mutations including divergent sequences saturated in synonymous sites.…”

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confidence: 99%

Assessing Uncertainty in the Rooting of the SARS-CoV-2 Phylogeny

Pipes

Wang

Huelsenbeck

et al. 2020

Molecular Biology and Evolution

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The rooting of the SARS-CoV-2 phylogeny is important for understanding the origin and early spread of the virus. Previously published phylogenies have used different rootings that do not always provide consistent results. We investigate several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. We show that methods based on the molecular clock tend to place the root in the B clade, whereas methods based on outgroup rooting tend to place the root in the A clade. The results from the two approaches are statistically incompatible, possibly as a consequence of deviations from a molecular clock or excess back-mutations. We also show that none of the methods provide strong statistical support for the placement of the root in any particular edge of the tree. These results suggest that phylogenetic evidence alone is unlikely to identify the origin of the SARS-CoV-2 virus and we caution against strong inferences regarding the early spread of the virus based solely on such evidence.

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A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein

Cited by 79 publications

References 0 publications

A novel SARS-CoV-2 related coronavirus in bats from Cambodia

A novel SARS-CoV-2 related coronavirus in bats from Cambodia

Emergence of Bat-Related Betacoronaviruses: Hazard and Risks

Assessing Uncertainty in the Rooting of the SARS-CoV-2 Phylogeny

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