Nature: Find high affinity neutral antibodies! COVID-19 treatment back to the antibody era!

, June 29, 2020 /
PRNewswire-BIOON/ -- Scientists around the world are stepping up efforts to use antibodies as a treatment for COVID-19A study has revealed what can be gained from antibodies produced by patients with coronavirus infections that cause SARSCOVID-19 pandemic is the biggest public health crisis in a century, and it is imperative to develop medical interventions to combat SARS-CoV-2 coronavirusWriting in the journal Nature, Pinto et alprovides the evidence needed to take the crucial first step in the development of antibody immunotherapythe level of protection provided by theimmune system against SARS-CoV-2 exposure and infection is a hotly debated topicThe immune system's main response to this infection is to produce antibodies that recognize the virusOf particular note is the antibody's binding to a protein on the surface of the virus called a stingproteinCoronaviruses are named after their unique coronavirus silhouettes, which are caused by these proteinsantibodies that identify and bind to the virus's "stinging" block their ability to bind to ACE2 receptor proteins on human cellsThe interaction between the stingprotein and ACE2 is part of the process by which the coronavirus enters human cellsAs a result, antibodies that block the function of the stingprotein, called neutralizing the antibody, block infectionphoto source: Natureon the SARS-CoV-2 immune response, there is much to know However, it is becoming increasingly clear that antibodies extracted from the serum of COVID-19 recovering patients can be treated by infusion to other patients This "rehabilitation serum" method is very attractive, especially as an instant treatment option This is because more traditional treatments, such as drugs or vaccines, are unlikely to be available for some time A more high-tech way to use recovery serum is to manipulate antibody-producing B cells extracted from the blood of patients with COVID-19 or other coronavirus infections Each B cell produces a unique antibody, and a clone of an interested B cell can be used to produce the same specific required antibody, called monoclonal antibody to speed up the development of treatment, Pinto and his colleagues "went back in time" and turned to B-cell samples collected from people infected with the SARS-CoV coronavirus The virus, similar to SARS-CoV-2, triggered an outbreak of a disease called Severe Acute Respiratory Syndrome (SARS) in 2003 The hope of this approach is that the similarity between the two viruses could mean that some antibodies that can identify SARS-CoV can also identify and neutralise SARS-CoV-2 the "head", or receptor binding region (called S1), the "head" of the stingprotein, is the protein region where antibodies are most easily bound However, this region exists in different dynamic states, and the debate over whether it is "hidden" by the shell of carbohydrate molecules and not noticed by the immune system has begun Therefore, identifying functional antibodies that target the region is not a simple process Pinto et al combined blood cells in patients recovering from SARS in 2004 and 2013 and looked for antibodies that could identify SARS-CoV-2 Of the 25 different monoclonal antibodies mentioned by the authors, four identify receptor binding domains of SARS-CoV and SARS-CoV-2 stingproteins One of the antibodies, named S309, showed a high affinity with the domain during in vitro testing and was chosen for further study Pinto and colleagues used cryogenic electron microscopes to observe the interaction between the S309 antibody and the SARS-CoV-2 stingprotein This suggests that S309 binds to a close position in the stingprotein receptor binding region, where there is a carbohydrate molecule This area is not a key area that is directly integrated with ACE2 The sites identified by S309 are evolutionaryly conservative and similar to a series of bat coronaviruses and SARS-like coronaviruses This increases the likelihood that the antibody will have broad applicability against the virus in take part Therefore, this antibody is not only important in studying ways to control the COVID-19 pandemic in the coming years, but it could also be considered for use to prevent future outbreaks if the animal virus can quickly cause human infection in the end, effective treatment sourcing COVID-19 seems unlikely to rely on a single antibody Conversely, as in sars, a collaborative approach to binding different monoclonal antibodies in an antibody mixture may be more effective Moving these methods forward requires the availability of evidence of effective antibody neutralization from in vitro studies, as well as data from the body to assess the extent to which an antibody promotes other aspects of the immune response -- for example, by recruiting other immune cells to respond to infection There are many promising avenues to explore in these efforts Pinto and his colleagues have led the way in studying existing antibodies, and now they should have more B-cells to dig Many other teams have also made useful discoveries in finding antibodies that can target SARS-CoV-2 The next step will be to test individual antibodies and antibody mixtures in animal models to determine whether they are protective and then evaluate their safety and efficacy in human clinical trial The accelerated path may shorten the time interval between antibody discovery and human proof-of-concept trials to 5 or 6 months the latest prominent example of immunotherapy treatment of infectious diseases related to the fight against the Ebola virus Along with vaccines and traditional small-molecule drug trials, rapid progress has been made in the development of Ebola monoclonal antibody therapy A hybrid antibody called ZM app is continuing to be developed, targeting two key areas of the Ebola virus's key protein GP This advance in the fight against the Ebola virus offers hope for similar immunotherapy for SARS-CoV-2 Pinto and his colleagues' work marks an important step toward long-awaited and much-needed success (BioValleyBioon.com) references: Robbiani, D.F., Gaebler, C., Muecksch, F et al.
Convergent antibody responses to SARS-CoV-2 in convalescent individuals Nature (2020) https://doi.org/10.1038/s41586-020-2456-9
Pinto, D., Park, Y., Beltramello, M et al Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody Nature (2020) Back in time for an antibody to fight COVID-19
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