Coronavirus Series – Part 3: A Superantigenic Region in SARS-CoV-2 Spike and Its Immunotherapeutic Consequences: Lessons Learned from Recent Computations and Experiments
Wednesday, February 3, 2021
2:00 pm – 3:15 pm ET
Ivet Bahar, PhD - Distinguished Professor & John K. Vries Chair, Department of Computational & Systems Biology, School of Medicine, University of Pittsburgh
Dr. Bahar and her co-authors (listed below) recently discovered1 a superantigenic region on the spike protein of SARS-CoV-2, whose sequence and structure characteristics closely resemble those of a bacterial toxin, staphylococcal enterotoxin
B (SEB), known to cause toxic shock syndrome (TSS). The similarity between this superantigenic region and SEB led them to hypothesize that (i) multisystem inflammatory syndrome (MIS) observed in children as well as adults with severe Covid-19, which
shows same symptoms as TSS, could be caused by this region2 and (ii) anti-SEB monoclonal antibodies could be used for neutralizing this region. Among anti-SEB monoclonal antibodies they identified one, 6D3, that has been experimentally
verified to reduce SARS-CoV-2 infectivity3.
- Cheng MH, Zhang S, Porritt RA, Rivas MN, Paschold L, Willscher E, Binder M, Arditi M*, Bahar I* (2020) Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR
repertoire in patients with hyperinflammation. Proc Natl Acad Sci USA 117: 25254-25262
- Rivas MN, Porritt RA, Cheng MH, Bahar I, Arditi M. (2020) COVID-19
Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Novel
Disease that Mimics Toxic Shock Syndrome. The Superantigen Hypothesis. J Allergy Clin Immunol. S0091-6749: 31414-7.
- Cheng MH, Porritt RA, Rivas MN, Krieger JM, Ozdemir AB, Garcia G, Arumugaswami V, Fries BC, Arditi M, Bahar I. (2020) A Monoclonal
Antibody Against Staphylococcal Enterotoxin B Superantigen Inhibits SARS-CoV-2
entry in vitro. BioRxiv doi: https://doi.org/10.1101/2020.11.24.395079
Cheng MH1, Zhang S1, Porritt RA2,3, Rivas MN2,3, Paschold L4, Willscher E4, Binder M4, Krieger JM1, Ozdemir AB2,3, Garcia G5, Arumugaswami V5,
Fries BC6, Arditi M2,3 and Bahar I1
1 Department of Computational and Systems Biology, School of
Medicine, University of Pittsburgh, Pittsburgh, PA 15213.
of Pediatrics, Division of Pediatric Infectious Diseases and Immunology,
Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai
Medical Center, Los Angeles, CA 90048.
of Internal Medicine IV, Oncology/Hematology, Martin Luther University
Halle-Wittenberg, 06120 Halle (Saale), Germany.
5 Department of
Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los
Angeles, CA 90095, USA
6 Department of Medicine, Stony Brook
University Hospital, Stony Brook, New York, 11794, USA