Researchers from the Institute of Microbiology of the Chinese Academy of Sciences (IMCAS) have studied a new variant of the SARS-CoV-2 virus called BA.3.2.2, which they have labeled RE.2.2. The study, led by Prof. Gao George Fu's team at IMCAS, was published in the Proceedings of the National Academy of Sciences (PNAS). This variant shows some unique features, such as a stronger ability to bind to the human ACE2 receptor — a protein that the virus uses to enter human cells — and a different way of evading antibodies. It also has a new site where a sugar molecule (glycan) is attached to the spike protein, which is a key part of the virus's structure. The researchers found that a specific mutation, called R493Q, helps the virus bind more tightly to the ACE2 receptor by forming an extra hydrogen bond. They also tested how RE.2.2 interacts with ACE2 proteins from various animals and found that its ability to infect different species is similar to other omicron variants. This suggests that the virus may have a broad host range, potentially increasing its transmission potential. In experiments using pseudoviruses (non-infectious versions of the virus), scientists observed that RE.2.2 evades many types of antibodies. However, some antibodies that had lost effectiveness against earlier omicron variants were able to neutralize RE.2.2 again. This was attributed to a key change in the virus's spike protein, known as G446D, which appears to help antibodies bind better. The study suggests that the virus's evolution in terms of immune evasion is limited by its structural constraints. Using advanced techniques such as liquid chromatography–tandem mass spectrometry (LC-MS/MS) and cryo-electron microscopy (cryo-EM), the team identified up to 26 sites on the spike protein where sugar molecules are attached. One of these is a new site at position N529 on the receptor-binding domain (RBD) of the spike protein, which was not previously seen in SARS-CoV-2 variants. This change helps stabilize the spike protein in a closed shape, which may help balance the virus's strong binding to the ACE2 receptor with controlled entry into cells. The study also supports a rule in protein glycosylation called the "O-follows-N" rule, showing that the arrangement of sugars on the spike protein is highly organized.