The Investigation of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity by NIFDC researchers published in Cell


COVID-19 's pandemic has posed a great impact on human health and the global economy. SARS-CoV-2 is the pathogen that caused this pandemic. SARS-CoV-2, as an RNA virus, has a high mutation frequency. The S protein of SARS-CoV-2 is not only the key protein affecting virus infection, but also the main protein in the development of vaccines and therapeutics. The mutations of S protein have become the focus of academia and industry. Moreover, as a high-glycosylated protein, S protein contains 22 glycosylation sites. The glycosylation status of vaccines prepared in different expression systems may be different. At present, the most concerned issues are whether the mutations of S protein and glycosylation affect the infectivity and antigenicity of the virus, which might influence the protective effect of candidate vaccines and monoclonal antibodies.

Youchun Wang 's team in National Institutes for Food and Drug Control (NIFDC) used pseudovirus technology to construct a SARS-COV-2 pseudovirus library containing different mutants and strains with different glycosylation modifications, including 106 different pseudoviruses, and evaluated their infectivity and susceptibility to monoclonal neutralizing antibody and convalescent patient serum was evaluated, and it was found that: 1. Compared with the Wuhan-1 strain reported for the first time in China, the global prevalence D614G mutant (aspartic acid in position 614 changed to glycine) at S protein has reached more than 70%. Studies have shown that D614G mutation alone and D614G combined with other amino acids changes, such as D614G+L5F, D614G+V341I, D614G+K458R, D614G+I472V, D614G+D936Y, D614G+S939F and D614G+S943T, increase the infectivity of the pseudotyped viruses by more than 4 times, some as high as ten times. 2. Some glycosylation deletion mutations can significantly reduce the infectivity of the virus, indicating that viral infection depends on some glycans in S protein. 3. The mutation of some sites, such as N234Q, L452R, A475V, V483A and F490L, could significantly reduce the neutralizing susceptibility of monoclonal neutralizing antibodies. 4. Although the neutralization susceptibility of the mutants to the convalescent serum of the patient did not change by more than 4 times, they are statistically significant and deserve further attention.

This work provides a new method for studying the infectivity of SARS-CoV-2 and a technical approach to evaluate whether COVID-19 vaccine and therapeutic monoclonal antibody can effectively protect virus mutants. Close attention should be paid to the mutations that increase the infectivity of the virus and decrease the sensitivity to neutralizing antibodies. It plays an important role in the design and evaluation of COVID-19 vaccine and therapeutics.

Youchun Wang 's team has been engaged in pseudotyped virus research on emerging and reemerging infectious diseases for a long time. The largest pseudovirus library was constructed, including HIV-1, Ebola virus, Marburg virus, Nipah virus and Rift Valley fever virus, etc., containing more than 1200 pseudoviruses. It provides an important tool for the infectivity analysis of emerging and reemerging viruses and related vaccines and treatment products evaluations.