Functional reconstitution of the MERS CoV receptor binding motif. (May 2022)

• Record Type: Journal Article
• Authors: Uppalapati, Lakshminarasaiah; Roitburd-Berman, Anna; Weiss-Ottolenghi, Yael; Graham, Barney S.; Dimitrov, Dimiter S.; Ying, Tianlei; Failayev, Hila; Tsfadia, Yossi; Gershoni, Jonathan M.
• Is Part Of: Molecular immunology. Volume 145(2022)
• Page Start: 3
• Page End: 16
• Publication Date: 2022-05
• Subjects: MERS CoV Middle East Respiratory Syndrome Corona Virus -- SARS CoV Severe Acute Respiratory Syndrome Corona Virus -- ECDC European Centre for Disease Prevention and Control -- IACUC Institutional Animal Care and Use Committee -- FAO Food and Agriculture Organization of the United Nations -- UAE United Arab Emirates -- RBM Receptor Binding Motif -- mAbs monoclonal antibodies -- MBP maltose binding protein -- GST gutathione-S-transferase -- TBS Tris Buffered Saline -- TBST Tris Buffered Saline with Tween-20 -- PCR Polymerase Chain Reaction -- NGS Next Generation Sequencing -- ACE2 angiotensin converting enzyme 2 -- huDPP4 human dipeptidyl peptidase 4 -- gBlock gene block; Coronavirus -- COVID-19 -- MERS CoV -- Epitope-based vaccine -- Combinatorial phage display -- Epitope reconstitution; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.03.006
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: In the early 1960's the first human coronaviruses (designated 229E and OC43) were identified as etiologic agents of the common cold, to be followed by the subsequent isolation of three more human coronaviruses similarly associated with cold-like diseases. In contrast to these "mild" coronaviruses, over the last 20 years there have been three independent events of emergence of pandemic severe and acute life-threatening respiratory diseases caused by three novel beta-coronaviruses, SARS CoV, MERS CoV and most recently SARS CoV2. Whereas the first SARS CoV appeared in November 2002 and spontaneously disappeared by the summer of 2003, MERS CoV has continued persistently to spill over to humans via an intermediary camel vector, causing tens of cases annually. Although human-to-human transmission is rare, the fatality rate of MERS CoV disease is remarkably higher than 30%. COVID-19 however, is fortunately much less fatal, despite that its etiologic agent, SARS CoV2, is tremendously infectious, particularly with the recent evolution of the Omicron variants of concern (BA.1 and BA.2). Of note, MERS CoV prevalence in camel populations in Africa and the Middle East is extremely high. Moreover, MERS CoV and SARS CoV2 co-exist in the Middle East and especially in Saudi Arabia and the UAE, where sporadic incidences of co-infection have already been reported. Co-infection, either due to reverse spill-over of SARS CoV2 to camels or in double infected humans could lead to recombination between the two viruses, rendering either SARS CoV2 more lethal or MERS CoV more transmittable. In an attempt to prepare for what could develop into a catastrophic event, we have focused on developing a novel epitope-based immunogen for MERS CoV. Implementing combinatorial phage-display conformer libraries, the Receptor Binding Motif (RBM) of the MERS CoV Spike protein has been successfully reconstituted and shown to be recognized by a panel of seven neutralizing monoclonal antibodies. Highlights: Reconstitution of the major neutralizing surface of the beta coronavirus MERS CoV. Phage-display conformer libraries screened with neutralizing monoclonal antibodies. Receptor Binding Motifs of coronaviruses as epitope-based immunogens.