Behind the cloud of “mutation” of the new corona virus: Experts say limited mutations have little impact on drug design

Since the outbreak of new coronary pneumonia, the virus “mutation” has always been a topic of concern. So far, a number of research institutions have carried out research on this. What does a virus mutation mean? Will it lead to changes in the mechanisms of disease and challenges to the development and use of drugs and vaccines? became a cause of concern. While many people are concerned about “virus mutations,” several experts say the current mutation strains of the new coronavirus are very limited.

Yang Zhanqiu, director of the virus department at Wuhan University School of Medicine, told Red Star News that at present, the mutation of the new coronavirus is very small and has little impact on drug design and testing reagents. At the same time, virus mutation strains can be used to determine the intergenerational relationship of the virus, thereby finding the source of the disease.

On 6 March, WHO encouraged countries through the media to provide virus samples to verify mutations. On the same day, at a press conference held by the State Council on joint defense and control, Zhou Qi, deputy secretary-general of the Chinese Academy of Sciences and a member of the Chinese Academy of Sciences, said that the virus mutation has been reported so far, but more cases are needed in the process of virus mutation and more in-depth study. “There is currently a unified deployment in China for virus variants and vaccine development, and the virus variants we have seen have not affected drug development, antibody preparation and vaccine preparation,” the cycle said.

Several papers focus on whether the virus mutates

Expert: RNA virus mutation is common, new coronavirus mutation is limited

“Virus mutations”, at first glance, are a little scary and can even trigger terrible associations. But if you know the knowledge, you will know that the biological world all the time “mutation”, this is a “neutral word”.

“Viruses, animals, plants, etc. change every minute. “In the course of our conversation, the cells in our bodies are likely to mutate, ” Dr. Yu Mingsheng of the Institute of Microbiology at Anhui Medical University’s School of Basic Medicine told Red Star News. As long as the cells are proliferating, there is a possibility of mutation. However, the chances of mutation in human cells are lower because DNA is a double-stranded structure that is relatively complex and, in most cases, correctable.”

As a simple life, viruses are prone to errors in the replication process, he said. But this is only relative to the human population, the virus replication process DNA is easy to change, resulting in protein coding changes. There are also classifications in viruses, and DNA viruses are stable relative to RNA viruses, such as hepatitis B viruses, which are not easily changed. The new coronavirus is the RNA virus, RNA’s single-stranded structure, determines that the replication process once the error occurred, the error will be retained. For example, influenza, HIV virus is RNA virus mutation probability is relatively high. Similarly, the new coronavirus is also an RNA virus.

On February 18, researchers at Yale University and the University of Sydney published an article stressing that when a virus is transmitted between different hosts, it is bound to mutate, but that mutation does not mean that the virus will produce abnormal and destructive new viral properties, according to the Daily Economic News.

On February 29th Brazilian and British scientists published their paper, “South America’s First New Coronary Virus Report,” in which they looked at two Brazilian patients with a history of travel to Italy and, after analyzing their viral genes, found that one of the virus genomes compared to the “Hu-1 reference strain” published in China. There are three mutation points, and in two cases there are two different sources of the virus.

So has the new coronavirus mutated? According to the online popular science magazine “Back to Park” combed, February 19, the Chinese Academy of Sciences Xishuangbanna Tropical Botanical Garden in the preprinted ChinaXiv uploaded research by analyzing the genome data of 93 samples found that only 120 nucleotide sites have mutations, these mutations are evenly dispersed in 10 coding areas. On February 25, Southern Medical University analyzed and compared the genetic sequences of 38 viruses and found that, with the earliest sequence as a reference, there were 117 site mutations, and the mutation sites were not concentrated and were relatively evenly distributed across the entire genome.

Meanwhile, the research team of Cheng Genhong of the University of California, Los Angeles, and Tan Wenjie, a researcher at the Cdc’s Virus Disease Prevention and Control Institute, and others published a study entitled “Mutation, Recombination and Insertion in the Evolution of the New Coronavirus” on March 2 on the preprintplatform bioRxiv. The team collected and analyzed 120 new coronavirus genome sequences, including the latest strains from 11 Chinese patients. The systematic development tree constructed by the study shows that the differences in gene sequence between different strains are very limited. Of the new coronaviruses with 30,000 bases, only a few have mutated.

The article “The Origin and Continuity of SARS-CoV-2” was published in the National Science Review by the Lu Jian Task Force of the School of Life Sciences of Peking University and the Cui Jie Group of the Pasteur Institute of the Chinese Academy of Sciences, according to the news report. By analyzing the evolution of the 103 new coronavirus whole genome symbits to date, the paper found that 149 mutation points have occurred in the strain, most of which have recently occurred. The study revealed that the new coronavirus has evolved into two subtypes, L and S. Of these, 101 belong to these two subtypes. In terms of proportion, the L subtype is more common to reach 70%, S subtype accounted for 30%.

According to the authors, according to the evolution of the new coronavirus, there may be a big difference in the propagation ability and the severity of the L subtype and the S subtype.

The paper says that the difference between the two subtypes is the 28144th point of the viral RNA genome, the L subtype is T base (for leucine, Leu), and the S subtype is C base (corresponding to ser). By comparing it with other coronaviruses, the authors found that the new s-type coronavirus was closer to the bat-sourced coronavirus in the evolutionary tree, leading to the conclusion that Type S is relatively old.

The L subtype is more common in the early stages of the outbreak in Wuhan, while the frequency of the L subtype has decreased since the beginning of January 2020. The authors argue that human intervention may exert greater selective pressure on the L subtype, without which the L subtype may be more aggressive and spread more quickly. On the other hand, because of the relatively weak selection pressure, the older and less aggressive S-type may increase in relative frequency. These findings mean that there is an urgent need for further comprehensive research in the context of genomic data, epidemiological data and the 2019 coronavirus disease patients’ clinical symptoms charted.

The above-mentioned research has attracted much attention because it suggests that the virus mutation has produced a new type of coronavirus with different subtypes, and their infectious nature is different.

However, some experts have expressed different opinions on the division of viral subtypes in the study.

On March 6, Yang Zhanqiu, director of the virus institute of Wuhan University School of Medicine and a doctoral tutor, told Red Star News that a certain percentage of the gene mutations of the general virus can be considered to be a subtype, and the current study shows that the proportion of genetic mutations of the new coronary virus is very small.

“It is common for one, several, dozens, or hundreds of nucleotides to change in the genome of a new coronavirus with 30,000 bases, ” he said. It’s not a big mutation, it can only be said. “It cannot be determined that it is a new subtype based solely on the number of nucleotide mutations. And according to the virus detection antigen and host adaptability changes, can be said to be a new subtype appear.”

The virus mutation is mainly determined by the internal cause of the Brazilian patient silife and Chinese patients infected with the virus is not much different

The new coronavirus in Brazilian patients who have not been to China has three different degrees from the virus gene published in Wuhan, is it possible to mutate the virus spread from region to region and species? Yu Mingsheng explained that the virus mutation is determined by the internal cause, the external cause induced.

The internal cause of virus mutation is the characteristics of the virus itself, including whether its genomic structure is DNA or RNA, and how the virus replicates. But the chances of a coronavirus mutate are relatively low compared to influenza and HIV, he said.

On external causes, the spread of viruses in different hosts can easily and cause mutations. “For example, between different species, people, bats, pangolins, in terms of body temperature alone, the virus in order to adapt to the host environment, itself will have a mutation.” Yu Mingsheng said that between different groups of people, because the population immunity differences, some people have strong immunity, the virus is under the pressure of choice, will also occur mutations. Other viruses mutate because of the pressure of the drug. “But even without these external causes, the virus mutates in nature. But this mutation is a random process with no directional screening.”

Yang Zhanqiu believes that the structure and host of the virus itself are two important factors affecting virus variation, and the change of natural environment has a certain effect on virus variation.

So is the difference between Brazilian and Chinese patients in egrown? Yu Mingsheng said that the virus in the transmission process of mutation is a normal phenomenon, as long as foreign patients or through the use of Chinese virus design accounting primer to detect, it shows that the virus does not exist much variation.

So can the trend of virus mutation be predictable? Yang Zhanqiu said that the virus mutation trend also has the structure and host of the virus. At present, the new coronavirus virus mutation will not be very fast, gene recombination is even less likely.

What is the effect of virus mutation?

Very high probability of mutation is very low, and it does not affect drug development and vaccine preparation.

So will the mutation of the new coronavirus affect the patient’s symptoms? “Sometimes it may be a key nucleotide or key protein of a virus, and a change in its coded nucleotide site can cause a change in its key amino acids,” he said. It is possible to change the virus from low pathogenicity to highly pathogenic. Influenza viruses have such a possibility, and coronaviruses certainly have the same possibility. But so far no reports have been found in this regard. “

But the specific symptoms alone from the study of the virus structure itself is difficult to draw conclusions, Yang Zhanqiu believes that different symptoms of the patient’s virus can be analyzed.

So will the virus mutation pose a challenge to existing drug treatments? Especially for whether some target drugs lead to loss of efficacy. The virus can only change the receptor and target if it mutates very largely, according to Yu Mingsheng. For now, the likelihood of this degree of variation is extremely low. But the virus mutation may pose some challenges to vaccine use, and “the difficulty in developing a vaccine for influenza and HIV is that the virus is constantly mutated”.

Yang Zhanqiu also believes that the virus mutation is mainly to affect the vaccine. However, the effect on drug design is less, because small molecule peptides are targeted at a target for the virus, but most drugs are targeted at the entire virus and not at a gene or a certain part of the virus.

Similarly, the current degree of mutation of the new coronavirus does not cause the virus’s antigen reagents and nucleic acid reagents to fail. For the emergence of “false negative” or “fuyang” situation, Yang Zhanqiu believes that the cause may still be related to the sampling of tests, there may be no symptoms of the patient, but there is a virus in the body. The sampling method results in inaccurate test results.

On March 6th, at a press conference of the State Council’s Joint Defense and Control, Zhou Qi, deputy secretary-general of the Chinese Academy of Sciences and a member of the Chinese Academy of Sciences, said that the virus mutation has been reported so far, but more cases are needed and more in-depth research is needed in the process of virus mutation.

“There is currently a unified deployment in China for virus mutation and vaccine development, and the virus variants we have seen have not affected drug development, antibody preparation and vaccine preparation,” Zhou qi said, actively observing the degree of virus mutation, and actively layout of scientific research projects.

Virus mutation monitoring requires multi-country collaboration, traceable virus variants

In a paper published by Cheng Genhong, a professor in the Department of Microbiology and Immunogenetics at the University of California, Los Angeles, and Tan Wenjie, a researcher at the CDC’s Virus Disease Prevention and Control Institute, and others, they note that to further confirm the genetic mutations of the new coronavirus, The researchers obtained 120 new coronavirus genome sequences uploaded on GISAID, the influenza virus data platform.

At present, the monitoring of virus variation is mainly through genetic sequence comparison. Yu Mingsheng told Red Star News that scientists around the world now have an open public platform, research institutions found new species, new viruses, new bacteria, scientists will upload their nucleic acid sequence series to the Internet, for other researchers around the world to learn, to understand, to reference this thing. So people in different countries find themselves with viruses that are endemic in their countries, comparing their genetic sequences with online data.

On March 6, the World Health Organization, in response to the Daily Economic News, called on all countries with confirmed cases to provide more sequences of virus genes in order to jointly conduct research into virus mutations.

At the same time, according to the virus mutation, can be used to determine the intergenerational relationship of the virus, looking for the source of the virus.

On February 20, Yu Wenbin, a researcher at the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, said in an article on the botanical garden’s official website that researchers from the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences, in conjunction with the South China Agricultural University and the Beijing Brain Center, collected a collection of various fields shared with GISAID in various fields around the world. The EpiFluTM database covers genomic data from 93 new coronavirus samples from 12 countries on four continents (as of February 12), which traces the source of infection and the path of spread through genome-wide data analysis.

The study found that the 93 samples received contained 58 octaves, with a single-fold from patients in the South China seafood market associated with H1, while samples of the older gene types, H3, H13 and H38, were from outside the South China Seafood Market. It can be seen that the south China seafood market’s new coronavirus is introduced from other places, in the market rapid spread spread to the market outside.

Currently, researchers around the world are still studying virus mutations and virus traceability.