Research, translation, editing, report : Gan Yung Chyan
/ KUCINTA SETIA
Image : Lab research. Picture courtesy of Caixin.
Recent research suggests that coronavirus from bats may provide the genetic backbone of SARS-CoV-2 (the virus of the disease COVID-19; covi, in short), and further recombination events with bats or other wild animals have allowed it to obtain S protein, RBD, and multibase splice sites.
Another "speciality" of covi has found analogs in nature. On 11 March 2020, a paper posted on the bioRxiv preprinted website stated that there are multiple amino acid insertions in the protease cleavage site between the two subunits of S protein, S1 and S2, which is not unique to covi, in a novel bat coronavirus the S protein of the virus RmYN02 also has a similar insertion. The research team believes that this result strongly proves that similar insertions can occur naturally, and that covi originates from multiple natural recombinations between viruses present in bats and other wild animals. The paper has not been peer reviewed.
The paper is entitled "A novel bat coronavirus reveals natural insertion of the S1/S2 cleavage site of the Spike protein and a possible origin of HCoV-19". Institutions participating in the study include Wuhan Institute of Virology of the Chinese Academy of Sciences, Shandong No. First Medical University, Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, Beijing Institute of Life Sciences of the Chinese Academy of Sciences, Institute of Microbiology of the Chinese Academy of Sciences and University of Sydney. Their research suggests that coronavirus from bats may provide the genetic backbone of covi, and further recombination events with bats or other wild animals have allowed it to obtain S protein, RBD, and multibase splice sites.
S protein is a membrane fusion protein. Currently, the first step in the invasion of many RNA virus infections is to bind to target cells through the virus's membrane fusion protein. A short sequence of "PRRA" in the S protein of SARS-CoV-2 and the R bases following it constitute a Furin protease cleavage site "RRAR". This insertion was thought to be an important mutation of covi, and neither previous SARS nor SARS-like viruses possessed this characteristic.
The research team also found an insertion of a short sequence "PAA" at the junction of two subunits S1 and S2 of the S protein of a bat virus from Yunnan. Although its "PAA" is not the same as "PRRA" of covi, it can be shown that they are a separate insertion event. Finding this insertion from a bat virus means that it is of natural origin, and covi acquired this property through some kind of recombination. On 23 January 2020, a study posted on the bioRxiv preprinted platform by Shi Zhengli's team from the Wuhan Institute of Virology of the Chinese Academy of Sciences showed that covi was 96% identical to the RaTG13 coronavirus found in Yunnan chrysanthemum horseshoe bats (Rhinolophus affinis). Therefore, bats are considered likely to be natural hosts of covi.
The “RRAR” sequence was first mentioned on 2 February. Researchers from Nankai University and Qilu Normal University published a paper on the Chinese Science Science and Technology Preprint Platform ChinaXiv, stating that they unintentionally found the "RRAR" sequence in the amino acid sequence at the junction between the S1 and S2 proteins of covi. It conforms to the recognition pattern of Furin restriction site "RXXR", and this mutation may enhance the ability of covi to spread.
Before, because the "PRRA" restriction site was only found on the coronavirus, some people thought that this might be caused by human intervention. In response, Alice Catherine Hughes, co-author of the bioRxiv paper and associate researcher at the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, told reporters at Caixin, "There is no evidence of human intervention. This virus is clearly derived from the origin and evolution of wild animals. "
When the reporter asked whether the unique "PRRA" restriction site of covi might come from the "PAA" of RmYN02, she said, "It's possible."
This bat virus from Yunnan comes from samples collected by the research team from May to October 2019, and they obtained 302 samples from 227 bats in Mengla County, Yunnan. After metagenomic sequencing, the research team initially screened 11 valid samples of feces of Malayan horseshoe bats (Rhinolophus malayanus) collected from 6 May to 30 July 2019. After further research, two bat coronavirus genome sequences were finally obtained. They are named RmYN01 and RmYN02. Among them, RmYN02 is more consistent with covi, so it was selected for research.
The results of the study showed that RmYN02 and NDV showed 93.3% identity in the whole genome, of which the lab gene had the highest identity, reaching 97.2%. However, this does not mean that it is similar to the new coronavirus. Instead, it has very low consensus on the important receptor binding domain (RBD), only 61.3%. The research team also found that the conserved disulfide bond is missing in RmYN02, which may reduce its binding to ACE2 and even cause non-binding, and the cell surface receptors of SARS virus and covi are both ACE2. Hughes said that the S protein was why they chose RmYN02 for their research.
RmYN02 is not more closely related to new coronaviruses than some coronaviruses previously discovered. In February, there were many studies that directed the intermediate host of covi to pangolins such as the study by a group of scholars on the coronavirus samples collected from the lung tissues of Malayan pangolins (Manis javanica) in a Guangdong wildlife research centre, which is posted on bioRxiv on 20 February 2020. In this study yet to be peer reviewed, in the receptor binding domain (RBD), they found that one coronavirus isolated from Manis javanica shows 100%, 98.2%, 96.7% and 90.4% amino acid identity with covi in the E, M, N and S genes.
The bioRxiv paper mentioned in the third paragraph of this report also analyzed the above-mentioned viruses from bats or pangolins, and finally concluded that the coronavirus from bats may provide the genetic backbone of covi, and further recombination events with bats or other wild animals have given it S Protein, RBD and multibase splice sites.
StayGate's Notes:
HCoV-19 is the proposed name for the virus SARS-CoV-2 that the researchers adopted for the paper "A novel bat coronavirus reveals natural insertion of the S1/S2 cleavage site of the Spike protein and a possible origin of HCoV-19". It is not a short form. Please refer to http://www.caixin.com/2020-03-06/101524891.html?sourceEntityId=101526576 for Shi Zhengli's explanation of this term.
The official name of the virus in the disease COVID-19 for public research and media use is SARS-CoV-2.
Refs :
Restriction site insertion event not unique, SARS-CoV-2 may originate from natural recombination, Huang Yanhao, Xu Luyi, Caixin.com, http://science.caixin.com/2020-03-10/101526576.html
A novel bat coronavirus reveals natural insertion of the S1/S2 cleavage site of the Spike protein and a possible origin of HCoV-19, Weifeng Shi etal, https://www.biorxiv.org/content/10.1101/2020.03.02.974139v3; https://doi.org/10.1101/2020.03.02.974139, 11 March 2020.
Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin, Zhengli-Shi etal, https://doi.org/10.1101/2020.01.22.914952, 23 January 2020; Nature, 10.1038/s41586-020-2012-7.
Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins, Kanpeng Xiao etal, https://doi.org/10.1101/2020.02.17.951335, 20 February 2020.
Further Ref :
http://www.caixin.com/2020-03-06/101524891.html?sourceEntityId=101526576
/ KUCINTA SETIA
Image : Lab research. Picture courtesy of Caixin.
Recent research suggests that coronavirus from bats may provide the genetic backbone of SARS-CoV-2 (the virus of the disease COVID-19; covi, in short), and further recombination events with bats or other wild animals have allowed it to obtain S protein, RBD, and multibase splice sites.
Another "speciality" of covi has found analogs in nature. On 11 March 2020, a paper posted on the bioRxiv preprinted website stated that there are multiple amino acid insertions in the protease cleavage site between the two subunits of S protein, S1 and S2, which is not unique to covi, in a novel bat coronavirus the S protein of the virus RmYN02 also has a similar insertion. The research team believes that this result strongly proves that similar insertions can occur naturally, and that covi originates from multiple natural recombinations between viruses present in bats and other wild animals. The paper has not been peer reviewed.
The paper is entitled "A novel bat coronavirus reveals natural insertion of the S1/S2 cleavage site of the Spike protein and a possible origin of HCoV-19". Institutions participating in the study include Wuhan Institute of Virology of the Chinese Academy of Sciences, Shandong No. First Medical University, Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, Beijing Institute of Life Sciences of the Chinese Academy of Sciences, Institute of Microbiology of the Chinese Academy of Sciences and University of Sydney. Their research suggests that coronavirus from bats may provide the genetic backbone of covi, and further recombination events with bats or other wild animals have allowed it to obtain S protein, RBD, and multibase splice sites.
S protein is a membrane fusion protein. Currently, the first step in the invasion of many RNA virus infections is to bind to target cells through the virus's membrane fusion protein. A short sequence of "PRRA" in the S protein of SARS-CoV-2 and the R bases following it constitute a Furin protease cleavage site "RRAR". This insertion was thought to be an important mutation of covi, and neither previous SARS nor SARS-like viruses possessed this characteristic.
The research team also found an insertion of a short sequence "PAA" at the junction of two subunits S1 and S2 of the S protein of a bat virus from Yunnan. Although its "PAA" is not the same as "PRRA" of covi, it can be shown that they are a separate insertion event. Finding this insertion from a bat virus means that it is of natural origin, and covi acquired this property through some kind of recombination. On 23 January 2020, a study posted on the bioRxiv preprinted platform by Shi Zhengli's team from the Wuhan Institute of Virology of the Chinese Academy of Sciences showed that covi was 96% identical to the RaTG13 coronavirus found in Yunnan chrysanthemum horseshoe bats (Rhinolophus affinis). Therefore, bats are considered likely to be natural hosts of covi.
The “RRAR” sequence was first mentioned on 2 February. Researchers from Nankai University and Qilu Normal University published a paper on the Chinese Science Science and Technology Preprint Platform ChinaXiv, stating that they unintentionally found the "RRAR" sequence in the amino acid sequence at the junction between the S1 and S2 proteins of covi. It conforms to the recognition pattern of Furin restriction site "RXXR", and this mutation may enhance the ability of covi to spread.
Before, because the "PRRA" restriction site was only found on the coronavirus, some people thought that this might be caused by human intervention. In response, Alice Catherine Hughes, co-author of the bioRxiv paper and associate researcher at the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, told reporters at Caixin, "There is no evidence of human intervention. This virus is clearly derived from the origin and evolution of wild animals. "
When the reporter asked whether the unique "PRRA" restriction site of covi might come from the "PAA" of RmYN02, she said, "It's possible."
This bat virus from Yunnan comes from samples collected by the research team from May to October 2019, and they obtained 302 samples from 227 bats in Mengla County, Yunnan. After metagenomic sequencing, the research team initially screened 11 valid samples of feces of Malayan horseshoe bats (Rhinolophus malayanus) collected from 6 May to 30 July 2019. After further research, two bat coronavirus genome sequences were finally obtained. They are named RmYN01 and RmYN02. Among them, RmYN02 is more consistent with covi, so it was selected for research.
The results of the study showed that RmYN02 and NDV showed 93.3% identity in the whole genome, of which the lab gene had the highest identity, reaching 97.2%. However, this does not mean that it is similar to the new coronavirus. Instead, it has very low consensus on the important receptor binding domain (RBD), only 61.3%. The research team also found that the conserved disulfide bond is missing in RmYN02, which may reduce its binding to ACE2 and even cause non-binding, and the cell surface receptors of SARS virus and covi are both ACE2. Hughes said that the S protein was why they chose RmYN02 for their research.
RmYN02 is not more closely related to new coronaviruses than some coronaviruses previously discovered. In February, there were many studies that directed the intermediate host of covi to pangolins such as the study by a group of scholars on the coronavirus samples collected from the lung tissues of Malayan pangolins (Manis javanica) in a Guangdong wildlife research centre, which is posted on bioRxiv on 20 February 2020. In this study yet to be peer reviewed, in the receptor binding domain (RBD), they found that one coronavirus isolated from Manis javanica shows 100%, 98.2%, 96.7% and 90.4% amino acid identity with covi in the E, M, N and S genes.
The bioRxiv paper mentioned in the third paragraph of this report also analyzed the above-mentioned viruses from bats or pangolins, and finally concluded that the coronavirus from bats may provide the genetic backbone of covi, and further recombination events with bats or other wild animals have given it S Protein, RBD and multibase splice sites.
StayGate's Notes:
HCoV-19 is the proposed name for the virus SARS-CoV-2 that the researchers adopted for the paper "A novel bat coronavirus reveals natural insertion of the S1/S2 cleavage site of the Spike protein and a possible origin of HCoV-19". It is not a short form. Please refer to http://www.caixin.com/2020-03-06/101524891.html?sourceEntityId=101526576 for Shi Zhengli's explanation of this term.
The official name of the virus in the disease COVID-19 for public research and media use is SARS-CoV-2.
Refs :
Restriction site insertion event not unique, SARS-CoV-2 may originate from natural recombination, Huang Yanhao, Xu Luyi, Caixin.com, http://science.caixin.com/2020-03-10/101526576.html
A novel bat coronavirus reveals natural insertion of the S1/S2 cleavage site of the Spike protein and a possible origin of HCoV-19, Weifeng Shi etal, https://www.biorxiv.org/content/10.1101/2020.03.02.974139v3; https://doi.org/10.1101/2020.03.02.974139, 11 March 2020.
Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin, Zhengli-Shi etal, https://doi.org/10.1101/2020.01.22.914952, 23 January 2020; Nature, 10.1038/s41586-020-2012-7.
Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins, Kanpeng Xiao etal, https://doi.org/10.1101/2020.02.17.951335, 20 February 2020.
Further Ref :
http://www.caixin.com/2020-03-06/101524891.html?sourceEntityId=101526576
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