TSRI scientists has found how an investigational therapy, called ZMapp, fights against Ebola virus. The study, described in Nature Microbiology, has revealed how one of the three antibodies in ZMapp therapy binds to a little-known protein of the virus. ZMapp is made by Mapp Biopharmaceuticals. ZMapp represents a cocktail of three monoclonal antibodies directed against the Zaire strain of Ebola virus responsible for the 2014 epidemic. The Ebola virus uses the GP gene to make two glycoproteins: the transmembrane-anchored, trimeric viral surface glycoprotein (GP) and the soluble, dimeric glycoprotein (sGP). GP is usually used as a target for antibody therapies because of its key role in attachment to and entry into host cells. Little is known about the structure and function of sGP, although Ebola virus makes abundant sGP during infection. sGP is secreted into the blood of patients. According to Prof Andrew Ward, lead researcher of the study, it’s significant to determine how to target sGP and GP properly. To do this, a clearer picture of the structure of the Ebola virus is required. High-resolution images of the virus will help reveal its vulnerable sites and therefore illustrate how therapies neutralize it. With the help of cryo-electron microscopy, TSRI researchers solved the detailed structure of Ebola virus and antibodies against it. They examined the interaction between the virus and the three antibodies in the investigational therapy. Previously, the researchers had explored these interactions. But the images they obtained had low resolution, and could not tell how exactly the antibodies bind to GP on the virus surface. Now, the clearer picture of Ebola virus and three antibodies of ZMapp could provide ways to improve potency. TSRI researchers further explored one of the antibodies, known as 13C6, which is capable of targeting sGP. Related protein of CusAb: Recombinant FGFR3. Scientists are puzzled about sGP's function. Most of what Ebola virus produces during infection is this type of protein. The small size of sGP makes it hard to study. TSRI researchers used antibodies like 13C6 to bind sGP, and then they were able to see the structure of both sGP and these antibodies. As therapeutic options for Ebola Virus Disease (EVD) are very limited, effective agents to fight the infectious disease are in urgent need. The experimental ZMapp therapy have been found beneficial in non-human primate models in previous research. ZMapp could be a very promising intervention for EVD.
