Tsinghua University makes great progress in the study of humanized antibody against MERS virus

So far, there have been no specific therapeutic drugs and preventive vaccines against MERS coronavirus clinically. A research team first used of protein crystallography method to resolve three-dimensional structure of the MERS coronavirus membrane protein and the receptor-binding domain of the human receptor extracellular domain of DPP4 compound, revealing the molecular mechanism of MERS coronavirus infecting cells. The researchers also further screened and got two fully human monoclonal antibody MERS-4 and MERS-27 against MERS coronavirus with high neutralizing capacity and they can effectively inhibit the infection and spread of MERS coronavirus. Recombinant protein also can be acquired in vitro and in vivo.

Its mechanism mainly interacts by blocking the receptor binding domain of a cell surface receptor. Through in-depth analysis of the structure and function, the research group revealed that two antibodies recognized viral surface membrane proteins, and the combination of these two antibodies can significantly improve the antiviral synergy and broad spectrum. This series of studies were respectively published on July 9, 2013 and April 30, 2014 in the journal Cell Research and the US Science sub-journal Science Translational Medicine published paper entitled "MERS coronavirus S protein with the human receptor surface dipeptidyl peptidase 4 composite structure" and "Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein". Internationally renowned virologist Albert Osterhaus and Dr. Bart Haagmans spoke highly of the research team's achievements in the same period of "Research Highlights" of the journal Science Translational Medicine, saying that "the humanized monoclonal antibodies they developed with neutralizing activity play an important role in the prevention and treatment of MERS coronavirus ", and "completely humanized antibody library and the screening technology cannot just be applied for the antibody research and development of anti-MERS coronavirus but also provides key platform technology and tools for research and development against other infectious agents antibodies."

Since the end of 2013, the research group has focused on research of second-generation anti-MERS coronavirus humanized monoclonal antibody MERS-4s and has made significant progress. In recent progress, they not only maintain a high affinity and neutralizing activity of the original antibody, but also made the antibody expression levels expected to increase by 10 times, laying a solid foundation for the further development of animal experiments and clinical applications. At the same time, the research group will also further optimize MERS-4s and MERS-27 antibody, and they are now constructing antibody with a double bispecific expression. Bispecific antibodies not only have efficient neutralizing activity but also can neutralize the virus mutant, and its performance in terms of broad spectrum antiviral will be significantly improved. There are also other types of proteins that play important roles in biology research, such as recombinant protein.