PMC:7205724 / 20480-23259 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7205724","sourcedb":"PMC","sourceid":"7205724","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7205724","text":"6 Development of a human monoclonal antibody (mAb)\n\n6.1 Targeting the S protein\n\n6.1.1 Hypothesis: A mAb against the binding domain of the virus can inhibit SARS-CoV2 infection\nRecently, hybridoma supernatants containing antibody repertoires from immunized transgenic mice that express the human immunoglobulin heavy and light chains and rat origin immunoglobulin constant regions were used to detect antibodies that can cross neutralize SARS-S and SARS-2-S [26]. One chimeric 47D11 H2L2 antibody displayed such a cross-neutralizing activity, decreased syncytia formation induced by SARS-S and SARS2-S, and could protect VeroE6 cells against SARS-S and SARS2-S pseudotyped virus [26]. It may lie in its similar affinities for interacting with the same domain of the S1 subunit, i.e., S1B, of each SARS-S and SARS-2-S.\n\n6.1.2 Rational: The chimeric 47D11 H2L2 might not be effective in human lung cells as it is in vitro\n47D11 carried a higher affinity for interacting with the S2 subunit of SARS-S than that of SARS-2-S. It is important that for both SARS-S and SARS-2-S, the binding of the 47D11 antibody to the target – the S1B domain – does not block the binding of S1B and S2 to ACE2 receptor [26]. By contrast, neutralizing antibodies that specifically target SARS-S could compete with S1B and S2 for binding to ACE2.\n\n6.2 Targeting pro-inflammatory cytokines\n\n6.2.1 Hypothesis: A mAb against IL6 can attenuate hyper inflammation\nTocilizumab, also known as atlizumab, is a humanized anti-human IL6 receptor antibody approved by FDA for several inflammatory and autoimmune diseases severe, such as cytokine release syndrome, rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systematic juvenile idiopathic arthritis. It is safe and effective for both adults and children two years of age and older.\n\n6.2.2 Rationale: Tocilizumab can treat lung injury in patients with critical and severe COVID-19\nIn the study [27], 21 patients with COVID-19 whose condition was severe or critical received one or two doses of Tocilizumab plus standard therapy. Patients who had a mean IL6 level of more than 100 pg/ml before tocilizumab treatment showed improvement in clinical symptoms and peripheral oxygen saturation and normalization for lymphocyte proportion and CRP levels. Also, lung lesion opacity was absorbed in 90% of patients. Neither serious adverse effects nor deaths occurred with tocilizumab treatment.\nThere are ongoing clinical trials for tocilizumab treatment in patients with moderate and severe COVID-19. Currently, the use of Tocilizumab is recommended for patients with COVID-19 who have warning signs of hyper inflammation, as can be measured by IL6, ferritin, platelet counts, inflammatory markers, and H score 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