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Author

Kizzmekia S. Corbett

Bio: Kizzmekia S. Corbett is a academic researcher from National Institutes of Health. The author has contributed to research in topic(s): Neutralizing antibody & Coronavirus. The author has an hindex of 31, co-authored 71 publication(s) receiving 12367 citation(s). Previous affiliations of Kizzmekia S. Corbett include Scripps Research Institute & University of North Carolina at Chapel Hill.

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Topics: Neutralizing antibody, Coronavirus, Antibody ...read more
Papers
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Open accessJournal ArticleDOI: 10.1126/SCIENCE.ABB2507
13 Mar 2020-Science
Abstract: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

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5,197 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2022483
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vacci...

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1,543 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2028436
Abstract: Background Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased inciden...

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Topics: Coronavirus (56%), Immunogenicity (51%)

619 Citations


Open accessJournal ArticleDOI: 10.1073/PNAS.1707304114
Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus that since its emergence in 2012 has caused outbreaks in human populations with case-fatality rates of ∼36%. As in other coronaviruses, the spike (S) glycoprotein of MERS-CoV mediates receptor recognition and membrane fusion and is the primary target of the humoral immune response during infection. Here we use structure-based design to develop a generalizable strategy for retaining coronavirus S proteins in the antigenically optimal prefusion conformation and demonstrate that our engineered immunogen is able to elicit high neutralizing antibody titers against MERS-CoV. We also determined high-resolution structures of the trimeric MERS-CoV S ectodomain in complex with G4, a stem-directed neutralizing antibody. The structures reveal that G4 recognizes a glycosylated loop that is variable among coronaviruses and they define four conformational states of the trimer wherein each receptor-binding domain is either tightly packed at the membrane-distal apex or rotated into a receptor-accessible conformation. Our studies suggest a potential mechanism for fusion initiation through sequential receptor-binding events and provide a foundation for the structure-based design of coronavirus vaccines.

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Topics: Coronavirus (60%), Neutralizing antibody (54%), Ectodomain (52%) ...read more

591 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2024671
Abstract: Background Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replica...

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Topics: Coronavirus (65%)

524 Citations


Cited by
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Open accessJournal ArticleDOI: 10.1126/SCIENCE.ABB2507
13 Mar 2020-Science
Abstract: The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

...read more

5,197 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2020.02.058
16 Apr 2020-Cell
Abstract: The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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Topics: Ectodomain (56%), Viral entry (55%), Epitope (53%) ...read more

4,968 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2034577
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

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4,222 Citations


Open accessJournal ArticleDOI: 10.1126/SCIENCE.ABB2762
Renhong Yan1, Yuanyuan Zhang1, Yaning Li2, Lu Xia1  +2 moreInstitutions (2)
04 Mar 2020-Science
Abstract: Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.

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Topics: Coronavirus (59%), Protein domain (52%)

2,888 Citations


Open accessJournal ArticleDOI: 10.1038/S41591-020-0820-9
01 Apr 2020-Nature Medicine
Abstract: SARS-CoV-2 is the seventh coronavirus known to infect humans; SARSCoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.

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2,880 Citations


Performance
Metrics

Author's H-index: 31

No. of papers from the Author in previous years
YearPapers
202128
202024
20194
20186
20173
20161

Top Attributes

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Author's top 5 most impactful journals

bioRxiv

22 papers, 944 citations

Science

4 papers, 5.2K citations

The New England Journal of Medicine

4 papers, 2.8K citations

Cell Reports

3 papers, 72 citations

Scientific Reports

3 papers, 448 citations

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