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Characterization of Critical Determinants of ACE2-SARS CoV-2 RBD Interaction.

التفاصيل البيبلوغرافية
العنوان: Characterization of Critical Determinants of ACE2-SARS CoV-2 RBD Interaction.
المؤلفون: Brown EEF; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Rezaei R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Jamieson TR; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Dave J; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Martin NT; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Singaravelu R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Crupi MJF; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Boulton S; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Tucker S; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Duong J; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Poutou J; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Pelin A; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Yasavoli-Sharahi H; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada., Taha Z; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Arulanandam R; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Surendran A; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Ghahremani M; Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada., Austin B; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Matar C; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada., Diallo JS; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Bell JC; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Ilkow CS; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada., Azad T; Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2021 Feb 25; Vol. 22 (5). Date of Electronic Publication: 2021 Feb 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Angiotensin-Converting Enzyme 2/*chemistry , Angiotensin-Converting Enzyme 2/*metabolism , COVID-19/*metabolism , COVID-19/*virology , SARS-CoV-2/*metabolism , Spike Glycoprotein, Coronavirus/*chemistry , Spike Glycoprotein, Coronavirus/*metabolism, Amino Acid Sequence ; Angiotensin-Converting Enzyme 2/genetics ; Antibodies, Neutralizing/immunology ; Antiviral Agents/pharmacology ; Binding Sites ; COVID-19/immunology ; HEK293 Cells ; Host Microbial Interactions ; Humans ; Models, Molecular ; Mutation ; Protein Binding ; Protein Interaction Domains and Motifs ; Receptors, Virus/chemistry ; Receptors, Virus/metabolism ; SARS-CoV-2/drug effects ; Sequence Alignment ; COVID-19 Drug Treatment
مستخلص: Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. In this study, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2, by utilizing our recently developed NanoBiT technology-based biosensor as well as pseudotyped-virus infectivity assays. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, efficacy of competitive inhibitors, as well as neutralizing antibody activity. We also look at the implications the mutations may have on virus transmissibility, host susceptibility, and the virus transmission path to humans. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.
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فهرسة مساهمة: Keywords: NanoLuc Binary Technology; SARS-CoV-2; angiotensin-converting enzyme 2; bioluminescence; drug development; receptor binding domain; spike protein; vaccine development
المشرفين على المادة: 0 (Antibodies, Neutralizing)
0 (Antiviral Agents)
0 (Receptors, Virus)
0 (Spike Glycoprotein, Coronavirus)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
تواريخ الأحداث: Date Created: 20210306 Date Completed: 20210317 Latest Revision: 20221207
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7956771
DOI: 10.3390/ijms22052268
PMID: 33668756
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms22052268