Reporter : Li Chenyang
Source : ScienceNet WebChat
Ref : http://news.sciencenet.cn/htmlnews/2020/4/438651.shtm
Translation, editing : Gan Yung Chyan
/ KUCINTA SETIA
On 19 April 2020, the team of academicians led by Li Lanjuan of the Chinese Academy of Engineering published a new research paper without peer review on the preprint platform medRxiv. The paper pointed out that the new coronavirus has appeared mutations that can actually affect the pathogenicity, and it is necessary to take these mutations into consideration for drug and vaccine research and development.
The main conclusion of the thesis:
The variation and diversity of SARS-CoV-2 (covi, in short) strains may be greatly underestimated.
Different mutant strains can differ up to 270 times in cytopathic effect and viral load.
A trinucleotide mutation can greatly enhance the replication rate and pathogenic ability of the virus. Patients with this mutation were found to remain nucleic acid positive for 45 days.
The researchers isolated live virus that could replicate from feces, which was different from previous reports.
Between 22 January 2020 and 4 February 2020, the researchers isolated the virus from 11 covi-infected patients admitted to the Affiliated Hospital of Zhejiang University. These patients ranged in age from 4 months to 71 years, and 10 of them had a history of exposure to Wuhan.
Epidemiological information of 11 patients
The researchers performed ultra-deep sequencing of these 11 patient-derived virus isolates and compared them with 1111 genome sequences in the GISAID database. A total of 33 mutations in the viruses isolated from these 11 patients were found, 19 of which were the new mutations discovered.
The researchers wrote:
Although in this study, we only analyzed the virus isolated from 11 patients, we still observed a rich diversity of variation.
... This shows that the true diversity of the covi strains is still greatly underestimated.
The new coronavirus has seen many mutations, and a considerable part of the mutations related to adaptability are enriched at the interface between the viral S protein and the human ACE2 receptor.
Then here comes the key question
Do these mutations have a functional effect on the pathogenicity of the virus?
As we all know, the symptoms of the covi infection are very complicated, and it is also related to the patient's age, physical condition and other factors. To objectively assess the impact of these mutations on the pathogenicity of the virus, the researchers decided to conduct an in vitro infection test.
They chose a cell line called Vero-E6, which has an ACE2 receptor that is very similar to human cells. They infected Vero-E6 cells with viruses from all 11 patients, collected cells at intervals and tested the viral load of the cells.
During the first 4 hours, the viral load of these cells remained stable, and virus replication rarely occurred at this time.
After 8 hours, the viral load from patients 6, 7, 9, 10, and 11 increased significantly.
After 24 hours, all viral loads except No. 2 and No. 7 increased significantly, and No. 10 and No. 11 were much faster than others.
It is worth noting that compared with No. 2, which has the strongest replication ability, and No. 2, which has the weakest replication ability, the viral load in 24 hours is nearly 270 times different.
So, the higher the viral load, does it mean the stronger the lethality of the cells?
The researchers found at 48 hours and 72 hours that the higher the viral load, the higher the pathological effect and mortality of the cells.
In the virus from patient 11, there was an unexpected trinucleotide mutation, and this mutation showed "strong" in subsequent experiments, greatly improving the replication rate and pathogenicity of the strain. In fact, this patient's virus test was positive and lasted for an amazing 45 days. The functional impact of this trinucleotide mutation is worthy of further study.
Finally, contrary to the recently reported "no live virus isolated in feces", the three virus isolates in this study were obtained from patient stool samples, suggesting that covi does indeed have the ability to replicate in stool.
Finally, the researchers called for the development of drugs and vaccines for covid treatment, as soon as possible to consider the impact of these cumulative mutations to avoid potential pitfalls.
Fortunately, as of the writing of this thesis, all 11 patients mentioned in the article have been discharged.
https://doi.org/10.1101/2020.04.14.20060160
Source : ScienceNet WebChat
Ref : http://news.sciencenet.cn/htmlnews/2020/4/438651.shtm
Translation, editing : Gan Yung Chyan
/ KUCINTA SETIA
On 19 April 2020, the team of academicians led by Li Lanjuan of the Chinese Academy of Engineering published a new research paper without peer review on the preprint platform medRxiv. The paper pointed out that the new coronavirus has appeared mutations that can actually affect the pathogenicity, and it is necessary to take these mutations into consideration for drug and vaccine research and development.
The main conclusion of the thesis:
The variation and diversity of SARS-CoV-2 (covi, in short) strains may be greatly underestimated.
Different mutant strains can differ up to 270 times in cytopathic effect and viral load.
A trinucleotide mutation can greatly enhance the replication rate and pathogenic ability of the virus. Patients with this mutation were found to remain nucleic acid positive for 45 days.
The researchers isolated live virus that could replicate from feces, which was different from previous reports.
Between 22 January 2020 and 4 February 2020, the researchers isolated the virus from 11 covi-infected patients admitted to the Affiliated Hospital of Zhejiang University. These patients ranged in age from 4 months to 71 years, and 10 of them had a history of exposure to Wuhan.
Epidemiological information of 11 patients
The researchers performed ultra-deep sequencing of these 11 patient-derived virus isolates and compared them with 1111 genome sequences in the GISAID database. A total of 33 mutations in the viruses isolated from these 11 patients were found, 19 of which were the new mutations discovered.
The researchers wrote:
Although in this study, we only analyzed the virus isolated from 11 patients, we still observed a rich diversity of variation.
... This shows that the true diversity of the covi strains is still greatly underestimated.
The new coronavirus has seen many mutations, and a considerable part of the mutations related to adaptability are enriched at the interface between the viral S protein and the human ACE2 receptor.
Then here comes the key question
Do these mutations have a functional effect on the pathogenicity of the virus?
As we all know, the symptoms of the covi infection are very complicated, and it is also related to the patient's age, physical condition and other factors. To objectively assess the impact of these mutations on the pathogenicity of the virus, the researchers decided to conduct an in vitro infection test.
They chose a cell line called Vero-E6, which has an ACE2 receptor that is very similar to human cells. They infected Vero-E6 cells with viruses from all 11 patients, collected cells at intervals and tested the viral load of the cells.
During the first 4 hours, the viral load of these cells remained stable, and virus replication rarely occurred at this time.
After 8 hours, the viral load from patients 6, 7, 9, 10, and 11 increased significantly.
After 24 hours, all viral loads except No. 2 and No. 7 increased significantly, and No. 10 and No. 11 were much faster than others.
It is worth noting that compared with No. 2, which has the strongest replication ability, and No. 2, which has the weakest replication ability, the viral load in 24 hours is nearly 270 times different.
So, the higher the viral load, does it mean the stronger the lethality of the cells?
The researchers found at 48 hours and 72 hours that the higher the viral load, the higher the pathological effect and mortality of the cells.
In the virus from patient 11, there was an unexpected trinucleotide mutation, and this mutation showed "strong" in subsequent experiments, greatly improving the replication rate and pathogenicity of the strain. In fact, this patient's virus test was positive and lasted for an amazing 45 days. The functional impact of this trinucleotide mutation is worthy of further study.
Finally, contrary to the recently reported "no live virus isolated in feces", the three virus isolates in this study were obtained from patient stool samples, suggesting that covi does indeed have the ability to replicate in stool.
Finally, the researchers called for the development of drugs and vaccines for covid treatment, as soon as possible to consider the impact of these cumulative mutations to avoid potential pitfalls.
Fortunately, as of the writing of this thesis, all 11 patients mentioned in the article have been discharged.
https://doi.org/10.1101/2020.04.14.20060160
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