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The new coronavirus SARS-CoV-2 caused the most destructive pandemic in nearly a century, COVID-19, and one of the unresolved scientific problems is the natural source of this virus.
Recently, researchers from Wuhan Institute of Virology, Chinese Academy of Sciences and University of Chinese Academy of Sciences submitted a paper on the preprint website BioRxiv entitled "Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor".
They reported the new SARS-CoV-2 related virus lineages identified in bats found in Tongguan Town, Mojiang County, Yunnan Province.
These viruses were sampled in 2015.
The location and the research team previously reported were from the Chinese chrysanthemum bat, and The RaTG13 line with 96.
2% genomic identity of SARS-CoV-2 is in the same location.
The corresponding authors of the paper are Shi Zhengli, director of the Research Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Deputy Director of Wuhan National Biosafety Laboratory (Level 4), and Zhou Peng, head of the Bat Virus Infection and Immunity Group of Wuhan Institute of Virology, Chinese Academy of Sciences.
The research and development also pointed out that, according to current research findings, none of the bat SARSr-CoV-2 or new lineage viruses that can be isolated so far cannot effectively use human ACE2.
Therefore, if there is no adaptation, the risk of spillover to humans is still relatively small.
In contrast, from the perspective of the use of recipients, pangolin coronavirus has a higher risk of spillage.
They also further emphasized that although previous speculations suggested that the leak of RaTG13 in the laboratory may have caused SARS-CoV-2, the existing experimental evidence does not support this speculation.
Shi Zhengli and others emphasized in this study that the SARS-like coronaviruses currently found in bats may be just the tip of the iceberg.
In the future, more systematic and vertical monitoring should be carried out to prevent the virus from causing major spills again.
Different from SARSr-CoV-1 and SARSr-CoV-2's new pedigree paper, it is stated that in May 2015, the research team conducted bat sampling in Mojiang County.
The bats were released after the anal swab was sampled, and the samples were stored at -80°C until use.
When tracking the origin of SARS-CoV-2 in bats, the research team had previously discovered RaTG13, which has 96.
2% genome homology with SARS-CoV-2, which is the closest genome to date.
When they further investigated the bat samples collected at the same location in 2015, they found that the sequence of 8 samples had 93.
5% homology with the SARS-CoV-2 sequence.
Seven were from the small brown chrysanthemum head bat (Rhinolophus stheno), and the other was from the middle chrysanthemum head bat (Rhinolophus affinis).
Therefore, they performed Next Generation Sequencing (NGS) to further analyze these coronaviruses, and all 8 samples obtained the whole genome sequence.
The 8 SARSr-CoV genomes are almost identical, and their sequence identity is over 99.
7%.
The research team performed further analysis with one of the virus strains named RaTG15 as a representative.
Among the seven conserved replicase domains used in the classification of coronaviruses, the homology of RaTG15 to SARS-CoV-2 and SARS-CoV-1 is 95.
3% and 92.
5%, respectively, indicating that it belongs to the Betacoronavirus genus of the coronavirus family.
The SARSr-CoV species in the subgenus Sarbecovirus.
In addition, RaTG15 is close to the SARS-CoV-2 gene in open reading frame 1b (ORF1b).
In the complete ORF1b region, the nucleotide sequence homology between RaTG15 and the wild bat SARSr-CoV-2 from China and Southeast Asia is 84.
6%-89.
0%, and the amino acid sequence homology is 95.
6%-97.
3%, which includes Bat coronaviruses RaTG13 and RmYN02 from Yunnan, Rc-o319 from Japan, RshSTT182 from Cambodia, RacCS203 from Thailand, and two pangolin coronavirus strains.
The study found that, in contrast, in addition to the aforementioned ORF1b, RaTG15 and SARSr-CoV-2 and SARSr-CoV-1 are significantly different in most genomes.
The gene homology of ORF1a, M and N is less than 80%, and the homology of S, ORF3, 6, and 7a/7b is less than 70%.
The study concluded that overall, the whole genome of RaTG15 has 74.
4% homology with SARS-CoV-1 sequence and 77.
6% with SARS-CoV-2 sequence.
It is worth noting that the sequence identity of RaTG15 and SARS-CoV-1 on S, E, M, N and ORF6 proteins is higher than that between RaTG15 and SARS-CoV-2.
The research team believes that this new virus lineage including RaTG15 may be the result of the recombination of different SARSr-CoVs.
The results of phylogenetic analysis also better support this point.
The research team pointed out that SARSr-CoVs were previously mainly composed of two sub-species, namely SARSr-CoV-1 and SARSr-CoV-2.
The latter include pangolins and SARS-CoV-2 in different species of chrysanthemum bats recently reported in many parts of Asia.
In the full-length gene tree and S gene tree, RaTG15 and its related viruses are far away from the two existing sub-lineages mentioned above, thus forming a new lineage.
Without further adaptation, the zoonotic potential is limited.
The researchers further tested the S protein sequence of RaTG15 and compared it with other SARSr-CoV-2. They found that the receptor binding domain (RBD) of the S protein of RaTG15 is highly different from other sarbecoviruses, having an amino acid homology of 72.
6% with SARS-CoV-2, and an amino acid homology with related bat and pangolin coronaviruses.
It is 68.
6%-73.
3%.
It is worth mentioning that, unlike the aforementioned RmYN02 and RacCS203, RaTG15 RBD does not have a deletion, which corresponds to the deletion of amino acids 473-486 in the SARS-CoV-2 S protein (deletion 2), according to In previous studies, this deletion determined the use of angiotensin-converting enzyme 2 (ACE2).
However, consistent with SARS-CoV-2 and RaTG13, a deletion corresponding to amino acids 444-447 (deletion 1) was found.
The missing position is similar to that of RshSTT182 in Cambodia.
In addition, among the 5 amino acid residues that SARS-CoV-2 binds to the ACE2 receptor, RaTG15 appears to be different (486, 493, 494, and 501).
In addition, like most bat SARSr-CoVs, there is no furin restriction site at the S1-S2 junction of RaTG15.
The paper mentioned that sequence analysis showed that RaTG15 virus may use ACE2 as an entry receptor, and the researchers also conducted further verification tests.
RBD proteins from SARS-CoV-2, SARS-CoV-1, RaTG13, pangolin-CoV-GD, pangolin-CoV-GX and RaTG15 were used, as well as the outer domains of human and middle chrysanthemum bat ACE2 proteins (Figure S2A).
They found that the RaTG13 and RaTG15 RBD proteins derived from the chrysanthemum head bat have weak or no binding affinity for human ACE2 (HuACE2).
The RBD proteins of the two pangolins SARSr-CoVs have much higher binding affinity to HuACE2, only slightly weaker than SARS-CoV-2 RBD, but still higher than SARS-CoV-1.
The binding affinity of pangolin-CoV-GX to HuACE2 is slightly weaker than that of pangolin-CoV-GD.
The researchers further verified whether the bat coronaviruses RaTG13 and RaTG15 can more effectively use the chrysanthemum bat ACE2 (RaACE2) than the use of huACE2? The results showed that the affinity of RaTG15 RBD to RaACE2 was also significantly lower than that of SARS-CoV-2 and pangolin-CoV-GD/GX to RaACE2.
As in HuACE2, the binding of RaTG13 RBD to RaACE2 is weak.
The researchers also conducted a fake virus infection test.
Consistent with the protein binding analysis of RBD-ACE2, HuACE2 mediates the entry of all SARSr-CoVs except RaTG15, while ACE2 supports the entry of all SARSr-CoVs.
The study concluded that neither the SARSr-CoV-2 lineage nor the new lineage virus identified this time can effectively bind HuACE2, and the absence of the RBD region seems to greatly affect the binding ability.
Researchers believe that these results indicate that if there is no further adaptation, bat-derived RaTG13, RaTG15 and other possible SARSr-CoV-2 viruses have limited zoonotic potential.
In contrast, from the perspective of the use of cell receptors, pangolin coronavirus has a higher risk of spillage.
Experimental evidence does not support laboratory leaks leading to SARS-CoV-2.
In general, the study reported a new SARSr-CoVs lineage discovered from bats.
These viruses are closely related to SARS-CoV-2 in the RdRp area.
However, it is still far from any known SARSr-CoVs at the genome level. The researchers pointed out that although several coronaviruses related to SARS-CoV-2 have been detected from wild animals, none of them are 99% genetically identical to SARS-CoV-2 at the genome level.
It should be noted that recombination events are more likely to occur between coronaviruses, which is also considered to be the potential origin of SARS-CoV-1.
In previous SARS traceability studies, the SARSr-CoVs found in bats carried all SARS-CoV-1 genome fragments.
Part of the genome regions of different wild animals are highly similar to the SARS-CoV-2 sequence, which also suggests that the virus may recombine during the evolution of viruses that spread across species or between species.
The researchers pointed out in the discussion section of the paper that their research results indicate that the SARSr-CoVs we now find from bats may be just the tip of the iceberg.
These viruses may have undergone selection or recombination events in animal hosts, allowing the viruses to adapt to new hosts and then spread to new species until they enter human society.
They emphasized that the new lineage virus identified this time should be monitored to prevent future outbreaks.
Because viruses from the other two lineages of SARSr-CoV, namely SARS-CoV-1 and SARS-CoV-2, caused SARS and COVID-19, respectively.
In addition, according to current research findings, none of the bat SARSr-CoV-2 or new lineage viruses that can be isolated so far cannot effectively use human ACE2.
Therefore, if adaptation is not carried out, the risk of spillover to humans is relatively small.
In contrast, viruses that can use ACE2 in the bat SARSr-CoV-1 related lineage seem to be more dangerous in terms of cross-species transmission.
The study mentioned that RaTG13 is the closest bat coronavirus to SARS-CoV-2, but it still only shows a weak binding affinity for HuACE2.
They emphasized that although there were previous speculations that the leak of RaTG13 in the laboratory may have caused SARS-CoV-2, the existing experimental evidence does not support this speculation.
In contrast, pangolin coronavirus has a strong binding ability to humans or bat ACE2, and has a high cross-species potential for humans or other species.
The researchers analyzed that in the context of SARS-CoV-2 originating from animals, there may be a bat SARSr-CoV that uses HuACE2 more effectively than RaTG13, or a pangolin coronavirus with higher genetic sequence identity.
The study finally emphasized that a more systematic and vertical sampling survey of bats, pangolins or other possible intermediate host animals is needed in the future to prevent future spills caused by SARSr-CoV related viruses, and to better understand SARS-CoV-2 origin of.
Link to the paper: 2020 hot articles selection 1.
Cup! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
"Feeling and rolling" for 28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight, and restored the old brain to a young state.
.
.
Recently, researchers from Wuhan Institute of Virology, Chinese Academy of Sciences and University of Chinese Academy of Sciences submitted a paper on the preprint website BioRxiv entitled "Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor".
They reported the new SARS-CoV-2 related virus lineages identified in bats found in Tongguan Town, Mojiang County, Yunnan Province.
These viruses were sampled in 2015.
The location and the research team previously reported were from the Chinese chrysanthemum bat, and The RaTG13 line with 96.
2% genomic identity of SARS-CoV-2 is in the same location.
The corresponding authors of the paper are Shi Zhengli, director of the Research Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Deputy Director of Wuhan National Biosafety Laboratory (Level 4), and Zhou Peng, head of the Bat Virus Infection and Immunity Group of Wuhan Institute of Virology, Chinese Academy of Sciences.
The research and development also pointed out that, according to current research findings, none of the bat SARSr-CoV-2 or new lineage viruses that can be isolated so far cannot effectively use human ACE2.
Therefore, if there is no adaptation, the risk of spillover to humans is still relatively small.
In contrast, from the perspective of the use of recipients, pangolin coronavirus has a higher risk of spillage.
They also further emphasized that although previous speculations suggested that the leak of RaTG13 in the laboratory may have caused SARS-CoV-2, the existing experimental evidence does not support this speculation.
Shi Zhengli and others emphasized in this study that the SARS-like coronaviruses currently found in bats may be just the tip of the iceberg.
In the future, more systematic and vertical monitoring should be carried out to prevent the virus from causing major spills again.
Different from SARSr-CoV-1 and SARSr-CoV-2's new pedigree paper, it is stated that in May 2015, the research team conducted bat sampling in Mojiang County.
The bats were released after the anal swab was sampled, and the samples were stored at -80°C until use.
When tracking the origin of SARS-CoV-2 in bats, the research team had previously discovered RaTG13, which has 96.
2% genome homology with SARS-CoV-2, which is the closest genome to date.
When they further investigated the bat samples collected at the same location in 2015, they found that the sequence of 8 samples had 93.
5% homology with the SARS-CoV-2 sequence.
Seven were from the small brown chrysanthemum head bat (Rhinolophus stheno), and the other was from the middle chrysanthemum head bat (Rhinolophus affinis).
Therefore, they performed Next Generation Sequencing (NGS) to further analyze these coronaviruses, and all 8 samples obtained the whole genome sequence.
The 8 SARSr-CoV genomes are almost identical, and their sequence identity is over 99.
7%.
The research team performed further analysis with one of the virus strains named RaTG15 as a representative.
Among the seven conserved replicase domains used in the classification of coronaviruses, the homology of RaTG15 to SARS-CoV-2 and SARS-CoV-1 is 95.
3% and 92.
5%, respectively, indicating that it belongs to the Betacoronavirus genus of the coronavirus family.
The SARSr-CoV species in the subgenus Sarbecovirus.
In addition, RaTG15 is close to the SARS-CoV-2 gene in open reading frame 1b (ORF1b).
In the complete ORF1b region, the nucleotide sequence homology between RaTG15 and the wild bat SARSr-CoV-2 from China and Southeast Asia is 84.
6%-89.
0%, and the amino acid sequence homology is 95.
6%-97.
3%, which includes Bat coronaviruses RaTG13 and RmYN02 from Yunnan, Rc-o319 from Japan, RshSTT182 from Cambodia, RacCS203 from Thailand, and two pangolin coronavirus strains.
The study found that, in contrast, in addition to the aforementioned ORF1b, RaTG15 and SARSr-CoV-2 and SARSr-CoV-1 are significantly different in most genomes.
The gene homology of ORF1a, M and N is less than 80%, and the homology of S, ORF3, 6, and 7a/7b is less than 70%.
The study concluded that overall, the whole genome of RaTG15 has 74.
4% homology with SARS-CoV-1 sequence and 77.
6% with SARS-CoV-2 sequence.
It is worth noting that the sequence identity of RaTG15 and SARS-CoV-1 on S, E, M, N and ORF6 proteins is higher than that between RaTG15 and SARS-CoV-2.
The research team believes that this new virus lineage including RaTG15 may be the result of the recombination of different SARSr-CoVs.
The results of phylogenetic analysis also better support this point.
The research team pointed out that SARSr-CoVs were previously mainly composed of two sub-species, namely SARSr-CoV-1 and SARSr-CoV-2.
The latter include pangolins and SARS-CoV-2 in different species of chrysanthemum bats recently reported in many parts of Asia.
In the full-length gene tree and S gene tree, RaTG15 and its related viruses are far away from the two existing sub-lineages mentioned above, thus forming a new lineage.
Without further adaptation, the zoonotic potential is limited.
The researchers further tested the S protein sequence of RaTG15 and compared it with other SARSr-CoV-2. They found that the receptor binding domain (RBD) of the S protein of RaTG15 is highly different from other sarbecoviruses, having an amino acid homology of 72.
6% with SARS-CoV-2, and an amino acid homology with related bat and pangolin coronaviruses.
It is 68.
6%-73.
3%.
It is worth mentioning that, unlike the aforementioned RmYN02 and RacCS203, RaTG15 RBD does not have a deletion, which corresponds to the deletion of amino acids 473-486 in the SARS-CoV-2 S protein (deletion 2), according to In previous studies, this deletion determined the use of angiotensin-converting enzyme 2 (ACE2).
However, consistent with SARS-CoV-2 and RaTG13, a deletion corresponding to amino acids 444-447 (deletion 1) was found.
The missing position is similar to that of RshSTT182 in Cambodia.
In addition, among the 5 amino acid residues that SARS-CoV-2 binds to the ACE2 receptor, RaTG15 appears to be different (486, 493, 494, and 501).
In addition, like most bat SARSr-CoVs, there is no furin restriction site at the S1-S2 junction of RaTG15.
The paper mentioned that sequence analysis showed that RaTG15 virus may use ACE2 as an entry receptor, and the researchers also conducted further verification tests.
RBD proteins from SARS-CoV-2, SARS-CoV-1, RaTG13, pangolin-CoV-GD, pangolin-CoV-GX and RaTG15 were used, as well as the outer domains of human and middle chrysanthemum bat ACE2 proteins (Figure S2A).
They found that the RaTG13 and RaTG15 RBD proteins derived from the chrysanthemum head bat have weak or no binding affinity for human ACE2 (HuACE2).
The RBD proteins of the two pangolins SARSr-CoVs have much higher binding affinity to HuACE2, only slightly weaker than SARS-CoV-2 RBD, but still higher than SARS-CoV-1.
The binding affinity of pangolin-CoV-GX to HuACE2 is slightly weaker than that of pangolin-CoV-GD.
The researchers further verified whether the bat coronaviruses RaTG13 and RaTG15 can more effectively use the chrysanthemum bat ACE2 (RaACE2) than the use of huACE2? The results showed that the affinity of RaTG15 RBD to RaACE2 was also significantly lower than that of SARS-CoV-2 and pangolin-CoV-GD/GX to RaACE2.
As in HuACE2, the binding of RaTG13 RBD to RaACE2 is weak.
The researchers also conducted a fake virus infection test.
Consistent with the protein binding analysis of RBD-ACE2, HuACE2 mediates the entry of all SARSr-CoVs except RaTG15, while ACE2 supports the entry of all SARSr-CoVs.
The study concluded that neither the SARSr-CoV-2 lineage nor the new lineage virus identified this time can effectively bind HuACE2, and the absence of the RBD region seems to greatly affect the binding ability.
Researchers believe that these results indicate that if there is no further adaptation, bat-derived RaTG13, RaTG15 and other possible SARSr-CoV-2 viruses have limited zoonotic potential.
In contrast, from the perspective of the use of cell receptors, pangolin coronavirus has a higher risk of spillage.
Experimental evidence does not support laboratory leaks leading to SARS-CoV-2.
In general, the study reported a new SARSr-CoVs lineage discovered from bats.
These viruses are closely related to SARS-CoV-2 in the RdRp area.
However, it is still far from any known SARSr-CoVs at the genome level. The researchers pointed out that although several coronaviruses related to SARS-CoV-2 have been detected from wild animals, none of them are 99% genetically identical to SARS-CoV-2 at the genome level.
It should be noted that recombination events are more likely to occur between coronaviruses, which is also considered to be the potential origin of SARS-CoV-1.
In previous SARS traceability studies, the SARSr-CoVs found in bats carried all SARS-CoV-1 genome fragments.
Part of the genome regions of different wild animals are highly similar to the SARS-CoV-2 sequence, which also suggests that the virus may recombine during the evolution of viruses that spread across species or between species.
The researchers pointed out in the discussion section of the paper that their research results indicate that the SARSr-CoVs we now find from bats may be just the tip of the iceberg.
These viruses may have undergone selection or recombination events in animal hosts, allowing the viruses to adapt to new hosts and then spread to new species until they enter human society.
They emphasized that the new lineage virus identified this time should be monitored to prevent future outbreaks.
Because viruses from the other two lineages of SARSr-CoV, namely SARS-CoV-1 and SARS-CoV-2, caused SARS and COVID-19, respectively.
In addition, according to current research findings, none of the bat SARSr-CoV-2 or new lineage viruses that can be isolated so far cannot effectively use human ACE2.
Therefore, if adaptation is not carried out, the risk of spillover to humans is relatively small.
In contrast, viruses that can use ACE2 in the bat SARSr-CoV-1 related lineage seem to be more dangerous in terms of cross-species transmission.
The study mentioned that RaTG13 is the closest bat coronavirus to SARS-CoV-2, but it still only shows a weak binding affinity for HuACE2.
They emphasized that although there were previous speculations that the leak of RaTG13 in the laboratory may have caused SARS-CoV-2, the existing experimental evidence does not support this speculation.
In contrast, pangolin coronavirus has a strong binding ability to humans or bat ACE2, and has a high cross-species potential for humans or other species.
The researchers analyzed that in the context of SARS-CoV-2 originating from animals, there may be a bat SARSr-CoV that uses HuACE2 more effectively than RaTG13, or a pangolin coronavirus with higher genetic sequence identity.
The study finally emphasized that a more systematic and vertical sampling survey of bats, pangolins or other possible intermediate host animals is needed in the future to prevent future spills caused by SARSr-CoV related viruses, and to better understand SARS-CoV-2 origin of.
Link to the paper: 2020 hot articles selection 1.
Cup! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
"Feeling and rolling" for 28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight, and restored the old brain to a young state.
.
.
