Wednesday, March 4, 2020

SARS-CoV-2 has evolved into two subtypes, based on samples collected till 5 February 2020

Ref : http://www.chinanews.com/gn/2020/03-04/9113340.shtml
Translation, editing : Gan Yung Chyan
                                  / KUCINTA SETIA

Image courtesy : CDC

The origin and evolution of SARS-CoV-2 (covi, in short) has received much attention. There are controversies as to whether the virus came from the Huanan seafood market, the wild animals that were illegally traded there and then transmitted to humans, and whether the market is the origin of COVID-19 (covid, in short).

On 3 March 2020, the National Science Review sponsored by the Chinese Academy of Sciences published a paper entitled "About the Origin and Continuous Evolution of SARS-CoV-2", which adopted the evolution of the largest genome of the covi to date. The analysis revealed that covi has evolved into two subtypes, L and S. The two subtypes are far away from each other in terms of geographical distribution and population. Based on the evolution of the new coronavirus, the authors speculate that there may be significant differences between the two subtypes in their transmission capacity and severity of disease.

L type virus has strong ability to spread, high pathogenicity

Researcher Lu Jian from the Centre for Bioinformatics, School of Life Sciences, Beijing University and Researcher Cui Jie from the Shanghai Pasteur Institute of the Chinese Academy of Sciences are co-corresponding authors of this paper. The author said: "If this conclusion is confirmed, it may guide us to better differentiate and treat covid."

All 103 genomic data of covi analyzed from the public database. The genetic sequence of these virus samples was collected as early as 24 December 2019 and as late as 5 February 2020. Analysis showed that there were 149 mutation sites in these virus strains, and most of the mutations occurred recently.

101 Of these 103 virus strains, 101 belong to one of the two subtypes. Specifically, the two subtypes differ in the 28144th position of the viral RNA genome, the L type is the T base (corresponding to leucine, Leu), and the S type is the C base (corresponding to serine, Ser). By comparing with other coronaviruses, the authors found that the S-type covi is closer to the bat-derived coronavirus on the phylogenetic tree, and concluded that the S-type is relatively older.

But researchers unexpectedly found that the relatively old S-type covi did not infect more people because it spread longer in the population. Genomic data showed that the proportion of S-type infections accounted for 30 per cent, but the relatively young L-type covid infection accounted for 70 per cent, and each L-type strain carried relatively more neonatal mutations than S-type.

Based on the above anomalies, the author speculates, "L-type viruses are more capable of transmitting or replicate faster in the human body, which may mean that their virulence is also greater."

The author also specifically compared the changes in the proportion of S-type and L-type before and after 7 January 2020. They found that the proportion of L-type in the virus strain decreased and the proportion of S-type increased. The author speculates, "This may be because patients with the L-type virus are more likely to show symptoms and therefore more susceptible to manual intervention. As a result, the negative selection pressure of the L-type coronavirus is greater, and the number of infected people is reduced accordingly. "

Patients can be infected with both L-type and S-type viruses

In addition, the 8872 and 28144 positions of the virus strains extracted from the vast majority of patients showed only C bases or T bases, that is, only one virus subtype of L or S was infected. However, a virus strain isolated from an American patient who had a recent travel history in Wuhan before the diagnosis was confirmed. These two loci showed a mixed phenomenon of C and T. In other words, it is likely that the patient was at the same time infected with L-type and S-type covid (but the possibility of new mutants cannot be ruled out at present).

A researcher working on bioinformatics analysis of the Chinese Academy of Sciences told First Financial Reporter, "The L-type appears to be a mutant type. From the preference of the two mutant codons of this subtype, it is more suitable for people, and it is more common in Hubei S type is a wild type, and the infection ability seems to be weak, but it is more widely distributed globally." He also said that because of the inconsistent gene sequencing technology, it may also lead to biased data analysis.

The author also specifically pointed out that an important corollary of the paper, that is, the relationship between different subtypes of the virus and their pathogenicity could have been strengthened by combining genomic data with case analysis. However, for various reasons, researchers cannot obtain patient data and cannot obtain more genomic data.

Previously, several scientific research teams found that the covid is similar to the SARS-associated coronavirus carried by bats, with a similarity of 96.2 per cent at the genome level. In this regard, the study authors of the above paper believe that, although previous studies have concluded that bat RaTG13 and covi differ only 4 per cent in the genome-wide nucleic acid sequence, a more meaningful comparison is to compare the differences in neutral loci on the genome. Through this comparison, they concluded that the difference between the covi and RaTG13 is much larger than the original understanding, and the genetic distance is 14 times the difference between humans and chimpanzees.

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