Study finds "dead hole" of SARS virus

Rapid mutations are thought to be the key to adapting the virus to environmental changes, but researchers at the University of North Carolina and Vanderbilt University have found that accelerated mutations instead affect the ability of SARS virus to cause disease in animals. The article, published in the journal Nature Medicine on November 11, opened up new ways for scientists to make safer live virus vaccines.

Researchers have modified the SARS coronavirus so that it lacks the ability to "proofread", that is, it cannot correct errors in replication. This makes the virus mutate faster, and it causes the virus to lose its ability to make mice pathogenic. Studies have shown that such modifications have greatly weakened the SARS virus.

During the SARS outbreak from 2002 to 2003, the mortality rate of adult patients was as high as 50%. Fortunately, under the effective control of the relevant parts, the epidemic was terminated in only four months. The total number of patients was 8,422, including 916. death. Recently, the public's nerves have tightened again, and new coronaviruses have emerged in the Middle East. The symptoms of these two new coronavirus infections include severe pneumonia and kidney failure. The disease caused one death. In this critical period, this research is particularly important.

In RNA viruses, replication fidelity is the key to determining their virulence and evading anti-viral attacks. "We thought the virus would repair or change the human mutation in some way. However, these modified viruses are quite stable and can allow the body to continue to produce a protective immune response. Even in low-immunity animals, it can be used as a perfect vaccine. "Rachel Graham, Ph.D., of the University of North Carolina, who led the study, said.

Researchers have worked hard for more than a decade to better understand the evolution and spread of coronavirus between species. They inactivated ExoN, an exonuclease as a correction protein, to obtain an attenuated strain of SARS virus. This virus cannot correct errors in replication, its mutation has increased by a factor of twenty, and it has lost its ability to cause disease.

Coronavirus is an RNA virus with the largest genome in the world of known RNA viruses. The ExoN correction protein maintains the coronavirus's large genome. It works with other proteins to help the virus survive and spread. Researchers now show that inactivated ExoN is a very promising vaccine development approach.

Researchers point out that live vaccines generally enable the body to produce wider and longer-term immunity, but the risk of live vaccines is that they may regain virulence in humans, such as polio vaccines in immunocompromised people. And their current results are very exciting, this attenuated vaccine for longer lasting effect is also safer. The researchers believe that this approach can also be applied to other important viruses to develop safer vaccines.

To test the possibility of this attenuated strain regaining virulence, the researchers allowed the virus to grow in hosts lacking immunity, including young, old, and immunosuppressed animals. Studies have shown that this virus cannot kill the host and the immune efficacy can last for a long time. The attenuated coronavirus obtained by inactivating ExoN is stable and will not regain virulence even if it is serially passaged in the body (long-term continuous infection).

The researchers pointed out that the evolution of the virus has strict control over its mutation rate, and changes in the mutation rate will affect the survival of the virus. The results of this research will have broad application prospects in the field of vaccine development.

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