Why is the New Coronavirus Omiljung variant more contagious? Shanghai scientists reveal the mechanism behind it

Due to the high frequency of mutations of the new crown virus, it continues to bring new challenges to the prevention and control of the global epidemic, especially the newly emerged Aomi Kerong mutation strain, which has caused a new round of infection peaks. Unlike the various mutant strains discovered in the past two years, the Number of Mutation Sites of the Semikron Strain is large, with as many as 37 mutations in the spike protein. However, neither these mutations affect the infectivity of the Omiljung strain nor the mechanisms that lead to immune escape. Recent studies have shown that a variety of current neutralizing antibodies against the new coronavirus are ineffective or significantly less potent against the Omiljung variant. Therefore, it is imperative to deeply understand the molecular mechanisms of transmission and infection of the Semikron variant and develop specific therapeutic antibodies against the Semikron variant.

Recently, the international authoritative academic journal "Science" published the latest research results jointly completed by Xu Huaqiang and Yin Wanchao of the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences and the cooperative units online. They analyzed the spike protein of the new coronavirus Omilon variant strain, as well as the high-resolution cryo-EM structure of the Omiljunn variant strain that binds to its receptor ACE2 and the broad-spectrum anti-COVID-19 antibody JMB2002, respectively, elaborated the molecular mechanism of rapid spread and immune escape of the Omiljung variant strain, and revealed a new mechanism of action for the therapeutic antibody JMB2002, providing new ideas for the design and development of broad-spectrum anti-COVID-19 antibodies.

Faced with the severe epidemic prevention and control situation, Xu Huaqiang and Yin Wanchao's team urgently tackled the problem and quickly analyzed the structure of the Omiljung mutant strain spike protein and the high-resolution cryo-EM structure that binds to the human receptor ACE2. Biochemical level experiments showed that the receptor ACE2 binding of the Aumequeron mutant strain had a significant enhancement compared with the wild type, nearly 10 times higher, and thermodynamic experiments showed that the receptor-binding domain of the Omiljun strain was highly flexible and unstable. This facilitates the interaction of the Opichron mutant spike protein with ACE2, explaining the underlying mechanism of enhanced infectivity of the Opichron mutant at the atomic level.

At the same time, the structure analyzed by the research team showed that most of the mutation sites of the Omiljung mutant's spike protein are located on the surface of the protein, including multiple antigen epitopes, which structurally explains the molecular mechanism by which the Omiljung variant can resist most of the neutralizing antibodies.

With the support of the cooperative unit, Xu Huaqiang and Yin Wanchao's team further analyzed the structure of the Omicron variant strain spike protein and the specific therapeutic antibody JMB2002. The antibody has completed phase I clinical trials and has a strong therapeutic effect and high safety. Biochemical level binding experiments showed that the antibody's binding power to the Spike Protein of the Omikejong mutant strain was 4 times that of the wild type, showing the potential to inhibit the Omiljung mutant strain.