Measles virus (MV) is the culprit of measles in children. According to statistics from the World Health Organization, approximately 20 million children worldwide suffer from measles each year. In 2010 alone, approximately 139,300 children died of measles virus infection. Measles virus is highly contagious and has a high incidence. In addition to causing common coughs, high fever, fear of light, and rashes all over the face, trunk, and upper extremities, it is also easy to be complicated by bronchopneumonia or meningitis, resulting in high mortality. Although the measles vaccine can effectively control the infection and spread of the measles virus, the measles vaccine is not perfect. Not only in countries and regions with low vaccine coverage, but also in countries with high coverage, such as Europe, America, and China, measles still causes death in children. One of the main reasons.
Measles virus belongs to the Paramyxoviridae family, which is spherical and is a negative-strand RNA virus with a capsule. The viral envelope contains Hemagglutinin (H) protein, which mediates the binding of host-specific receptor molecules, and is the most important molecule for initiating virus infection to cells. The cell adhesion molecule family member nectin-4 was recently identified as the measles virus receptor in epithelial cells, and became the third measles virus receptor molecule after SLAM and CD46. However, CD46 is only recognized by the measles vaccine strain; as a receptor for the virus-causing strain, nectin-4 has a wider tissue and organ distribution than SLAM. Therefore, identifying the binding mode of MV H protein and nectin-4 is of great significance for the study of measles virus invasion mechanism and the discovery of effective drug targets.
Gao Fu's research group of the Institute of Microbiology, Chinese Academy of Sciences has long been devoted to the study of the transspecies transmission mechanism and immune molecule recognition of enveloped virus. In response to the newly discovered virus receptor molecule, it has rapidly carried out functional studies on the structure and interaction of the complex. Researchers Zhang Xiaoai and Lu Guangwen from the Gaofu research group successfully prepared a protein complex of MV H and nectin-4 with high purity, obtained high-quality crystals, and analyzed the molecular structure of the complex. The MV H protein is a square structure composed of six propeller-like blades (β1-β6); the nectin-4 molecule binds to the β4 and β5 propellers of H protein through its first immunoglobulin-like domain. In the groove between the blades; the hydrophobic interaction is dominant between the two molecules. At the binding interface between nectin-4 and MV H, the nectin-4 molecule is inserted into a highly hydrophobic pocket of H protein through the Phe-Pro double residue motif at the top of the FG loop. Play a key role in mediating virus invasion.
Further comparative analysis revealed that this hydrophobic pocket also plays a very important role in the binding of MV H to the other two receptors SLAM and CD46. This suggests that designing small molecule drugs with this pocket as a target can effectively block the binding of measles virus to all the receptor molecules that have been identified.
The potential threat of measles to public health security urgently needs specific and highly effective anti-measles virus drugs. It is one of the most effective anti-virus means to block the combination and intrusion of viruses and prevent them from happening. The research group's research results on the combination mode of MV H and nectin-4 have important guiding significance for the design of drugs against measles virus.
The research results were recently published in the journal Nature Structural & Molecular Biology.
Electric Lint Remover,Rechargeable Foil Shaver,Rechargeable Fuzz Shaver,Electric Fabric Lint Remover
Ningbo Beilun Xuanfeng Molding Co., Ltd. , https://www.schelfern.com