Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.
Philip J. M. Brouwer,Tom G. Caniels,Karlijn van der Straten,Jonne L. Snitselaar,Yoann Aldon,Sandhya Bangaru,Jonathan L. Torres,Nisreen M.A. Okba,Mathieu Claireaux,Gius Kerster,Arthur E. H. Bentlage,Marlies M. van Haaren,Denise Guerra,Judith A. Burger,Edith E. Schermer,Kirsten D. Verheul,Niels van der Velde,Alex van der Kooi,Jelle van Schooten,Mariëlle J. van Breemen,Tom P. L. Bijl,Kwinten Sliepen,Aafke Aartse,Aafke Aartse,Ronald Derking,Ilja Bontjer,Neeltje A. Kootstra,W. Joost Wiersinga,Gestur Vidarsson,Bart L. Haagmans,Andrew B. Ward,Godelieve J. de Bree,Rogier W. Sanders,Rogier W. Sanders,Marit J. van Gils +34 more
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TLDR
It is shown that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell, and monoclonal antibodies isolated here are promising candidates for COVID-19 treatment and prevention.Abstract:
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.read more
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Current Trends in SPR Biosensing of SARS-CoV-2 Entry Inhibitors
Elba Mauriz,Laura M. Lechuga +1 more
TL;DR: In this paper, a review summarizes recent advancements in the drug discovery process of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) inhibitors using surface plasmon Resonance (SPR) biosensors.
Journal ArticleDOI
Perspectives on the use and risk of adverse events associated with cytokine-storm targeting antibodies and challenges associated with development of novel monoclonal antibodies for the treatment of COVID-19 clinical cases.
TL;DR: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel CoV-19 pandemic that lacks globally accessible effective antivirals.
Posted ContentDOI
Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung
Timothy Wu,Kyle J. Travaglini,Arjun Rustagi,Duo Xu,Yue Zhang,SoRi Jang,Astrid Gillich,Roozbeh Dehghannasiri,Giovanny J. Martínez-Colón,Aimee Beck,Aaron J. Wilk,Maurizio Morri,Winston Trope,Joseph B. Shrager,Stephen R. Quake,Christin S. Kuo,Julia Salzman,Peter S. Kim,Catherine A. Blish,Mark A. Krasnow +19 more
TL;DR: It is shown healthy human lung slices cultured ex vivo can be productively infected with SARS-CoV-2, and the cellular tropism of the virus and its distinct and dynamic effects on host cell gene expression can be determined by single cell RNA sequencing and reconstruction of “infection pseudotime” for individual lung cell types.
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Modular basis for potent SARS-CoV-2 neutralization by a prevalent VH1-2-derived antibody class
Micah Rapp,Yicheng Guo,Eswar R. Reddem,Lihong Liu,Pengfei Wang,Jian Yu,Gabriele Cerutti,Jude Bimela,Fabiana Bahna,Seetha Mannepalli,Baoshan Zhang,Peter D. Kwong,Peter D. Kwong,David D. Ho,Lawrence Shapiro,Zizhang Sheng,Zizhang Sheng +16 more
TL;DR: The structure of the SARS-CoV-2 spike was determined in complex with three VH1-2-derived antibodies: 2-15, 2-43, and H4 as mentioned in this paper.
Journal ArticleDOI
COVID-19 and immunity: quo vadis?
TL;DR: In this paper, the authors summarize what is currently known and unknown about the immune response during COVID-19 and discuss whether natural infections can lead to herd immunity, and discuss the possibility of natural infections leading to a herd immunity.
References
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Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
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