Science: Human monoclonal antibodies from recovering SRAS patients can cross neutralizing SARS-like coronaviruses.

, June 23, 2020 /
BiovalleyBIOON/coronavirus entering host cells is mediated by the virus's sting protein (S protein), which forms a tripolymer sting on the surface of the virusEach monomer in the triple-poly S protein assembly is a heterogenous dipolymer consisting of S1 and S2 subkeysThe S1 subkey consists of four domains: the N-end domain (NTD), the C-side domain (CTD), and the sub-domainiareas I and IIBoth SARS-CoV and SARS-CoV-2 CTD function as receptor binding domain (RBD) and are used to bind the same entry receptor --- human angiotensin transeronose 2 (hACE2)S2 subkeys contain fusion peptides, octapeptide repeat zones 1 and 2, and a trans-membrane domain, all of which are required for the fusion of viral and host cell membraneshuman coronavirus (HCoV) S protein is the main target of neutralizing antibodies (nAb)The S proteins of SARS-CoV and SARS-CoV-2 have 76% amino acid consistency, which raises the possibility that these antigens have conservative immunogenic surfacesStudies of recovery-period serums and a limited number of monoclonal antibodies (mAb) have shown limited intersecting neutralizing or non-intersectional neutralizing, confirming that conservative antigen sites are rarely targeted by nAbHowever, the frequency, specificity and functional activity of natural SARS-CoV and SARS-CoV-2 infection-induced cross-reactive antibodies are still not clearly determinedimages from Science, 2020, doi:10.1126/science.abc7424there is an urgent need for a widerange protective vaccine against known and emerging human coronaviruses (HCoVs)In a new study, U.Sresearchers analyzed a memory B cell pool for a recovering SRAS donor and found 200 SARS-CoV-2 binding antibodies that target multiple conservative sites on the surface of the S proteinThe findings were published online June 15, 2020 in the journal Science, under the title "Broad neutralization of SARS-related viruses by human human monoclonal antibodies"a large portion of these non-neutral antibodies show high levels of high-frequency mutations in somatic cells and cross-reactions to HCoV transmitted in the body, reminiscent of the prior presence of memory B cells caused by previous HCoV infectionsSeveral antibodies effectively intersect SARS-CoV, SARS-CoV-2 and bat SARS-like coronavirus WIV1 by blocking receptor attachment and inducing S1 sub-subgenic sheddingThese antibodies provide promising candidates for therapeutic interventions and provide targets for the rational design of the pan-sarbecovirus virus vaccinethese powerful cross-neutral and antibody-binding conservative epitopes overlap with hACE2 binding sites, revealing that this antigen surface is a promising target for the rational design of the Pansarbecovirus virus vaccineFor example, the RBD epitope identified by these antibodies can be presented on a structurally stable protein stent, thus concentrating the antibody reaction at this siteIn addition, these human antibodies, whether used alone or in combination, represent promising drug candidates that can be used to prevent or treat SARS, COVID-19, and potential future diseases caused by the emerging SARS-type coronavirus(Bio Valley Bioon.com)References:Anna ZWec etBroad neutralization of SARS-related viruses by human monoclonal antibodiesScience, 2020, doi:10.1126/science.abc7424.