scholarly journals Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

2020 ◽  
Vol 6 (45) ◽  
pp. eabc9999 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Full Length ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Novel Coronavirus

The current coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus genetically close to SARS-CoV. To investigate the effects of previous SARS-CoV infection on the ability to recognize and neutralize SARS-CoV-2, we analyzed 20 convalescent serum samples collected from individuals infected with SARS-CoV during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor binding domain (RBD) of SARS-CoV; cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2; and neutralized both SARS-CoV and SARS-CoV-2 S protein–driven infections. Analysis of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV verified cross-reactive neutralization against SARS-CoV-2. A SARS-CoV–derived RBD from palm civets elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing strategies for development of universal vaccines against emerging coronaviruses.

scholarly journals Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

2020 ◽  
Author(s):  
Yuanmei Zhu ◽  
Danwei Yu ◽  
Yang Han ◽  
Hongxia Yan ◽  
Huihui Chong ◽  
...  
Keyword(s):  
Public Health ◽  
Receptor Binding ◽  
Cross Reactivity ◽  
Social Stability ◽  
Receptor Binding Domain ◽  
Serum Antibodies ◽  
Serum Samples ◽  
S Protein ◽  
Palm Civet ◽  
Novel Coronavirus

AbstractThe current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs.SummarySerum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.

scholarly journals An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Yan Guo ◽  
Wenhui He ◽  
Huihui Mou ◽  
Lizhou Zhang ◽  
Jing Chang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Binding Domain ◽  
Full Length ◽  
Vaccine Antigen ◽  
Receptor Binding Domain ◽  
Protein Vaccine ◽  
Wild Type ◽  
S Protein ◽  
Glycosylation Sites

ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino-acid fragment of the 1,273-amino-acid S-protein protomer. The RBD is the primary SARS-CoV-2 neutralizing epitope and a critical target of any SARS-CoV-2 vaccine. Here, we show that this RBD conjugated to each of two carrier proteins elicited more potent neutralizing responses in immunized rodents than did a similarly conjugated proline-stabilized S-protein ectodomain. Nonetheless, the native RBD is expressed inefficiently, limiting its usefulness as a vaccine antigen. However, we show that an RBD engineered with four novel glycosylation sites (gRBD) is expressed markedly more efficiently and generates a more potent neutralizing responses as a DNA vaccine antigen than the wild-type RBD or the full-length S protein, especially when fused to multivalent carriers, such as a Helicobacter pylori ferritin 24-mer. Further, gRBD is more immunogenic than the wild-type RBD when administered as a subunit protein vaccine. Our data suggest that multivalent gRBD antigens can reduce costs and doses, and improve the immunogenicity, of all major classes of SARS-CoV-2 vaccines. IMPORTANCE All available vaccines for coronavirus disease 2019 (COVID-19) express or deliver the full-length SARS-CoV-2 spike (S) protein. We show that this antigen is not optimal, consistent with observations that the vast majority of the neutralizing response to the virus is focused on the S-protein receptor-binding domain (RBD). However, this RBD is not expressed well as an independent domain, especially when expressed as a fusion protein with a multivalent scaffold. We therefore engineered a more highly expressed form of the SARS-CoV-2 RBD by introducing four glycosylation sites into a face of the RBD normally occluded in the full S protein. We show that this engineered protein, gRBD, is more immunogenic than the wild-type RBD or the full-length S protein in both genetic and protein-delivered vaccines.

scholarly journals Roadmap to developing a recombinant coronavirus S protein receptor-binding domain vaccine for severe acute respiratory syndrome

2012 ◽  
Vol 11 (12) ◽  
pp. 1405-1413 ◽  
Author(s):  
Shibo Jiang ◽  
Maria Elena Bottazzi ◽  
Lanying Du ◽  
Sara Lustigman ◽  
Chien-Te Kent Tseng ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Protein Receptor

scholarly journals Structural Insights into Immune Recognition of the Severe Acute Respiratory Syndrome Coronavirus S Protein Receptor Binding Domain

2009 ◽  
Vol 388 (4) ◽  
pp. 815-823 ◽  
Author(s):  
John E. Pak ◽  
Chetna Sharon ◽  
Malathy Satkunarajah ◽  
Thierry C. Auperin ◽  
Cheryl M. Cameron ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
Immune Recognition ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Protein Receptor ◽  
Structural Insights

scholarly journals A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 724
Author(s):  
Paola Cristina Resende ◽  
Tiago Gräf ◽  
Anna Carolina Dias Paixão ◽  
Luciana Appolinario ◽  
Renata Serrano Lopes ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Binding Domain ◽  
The Other ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Other Hand

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

scholarly journals Predicting the Efficacy of COVID-19 Convalescent Plasma Donor Units with the Lumit Dx anti-Receptor Binding Domain Assay

2021 ◽  
Author(s):  
Sanath Kumar Janaka ◽  
Natasha M Clark ◽  
David T Evans ◽  
Joseph P Connor
Keyword(s):  
Receptor Binding ◽  
Therapeutic Option ◽  
Passive Immunization ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
S Protein ◽  
Antibody Assays ◽  
Antibody Titers ◽  
Novel Coronavirus ◽  
Design And Methods

AbstractBackgroundThe novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier.Study design and methodsSince virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx).ResultsAll measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays.DiscussionOur observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.

scholarly journals Durability of Viral Neutralization in Asymptomatic Coronavirus Disease 2019 for at Least 60 Days

2021 ◽  
Author(s):  
Amanda Haymond ◽  
Abdulla A Damluji ◽  
Aarthi Narayanan ◽  
Claudius Mueller ◽  
Alex Reeder ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Receptor Binding ◽  
Immunoglobulin G ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Serum Samples ◽  
Viral Neutralization ◽  
Time Period

Abstract A cohort consisting of asymptomatic healthcare workers donated temporal serum samples after infection with severe acute respiratory syndrome coronavirus 2. Analysis shows that all asymptomatic healthcare workers had neutralizing antibodies, that these antibodies persist for ≥60 days, and that anti-spike receptor-binding domain immunoglobulin G levels were correspondingly durable over the same time period.

scholarly journals Structures of synthetic nanobody–SARS-CoV-2–RBD complexes reveal distinct sites of interaction and recognition of variants

2021 ◽  
Author(s):  
David Margulies ◽  
Javeed Ahmad ◽  
Jiansheng Jiang ◽  
Lisa Boyd ◽  
Allison Zeher ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Crystal Structures ◽  
Receptor Binding ◽  
Ternary Complexes ◽  
Binding Domain ◽  
Structural Basis ◽  
Receptor Binding Domain ◽  
S Protein ◽  
X Ray ◽  
Binary And Ternary Complexes

Abstract The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emergence of new variants demands understanding the structural basis of the interaction of antibodies with the SARS-CoV-2 receptor-binding domain (RBD). Here we report five X-ray crystal structures of sybodies (synthetic nanobodies) including binary and ternary complexes of Sb16–RBD, Sb45–RBD, Sb14–RBD–Sb68, and Sb45–RBD–Sb68; and Sb16 unliganded. These reveal that Sb14, Sb16, and Sb45 bind the RBD at the ACE2 interface and that the Sb16 interaction is accompanied by a large CDR2 shift. In contrast, Sb68 interacts at the periphery of the interface. We also determined cryo-EM structures of Sb45 bound to spike (S). Superposition of the X-ray structures of sybodies onto the trimeric S protein cryo-EM map indicates some may bind both "up" and "down" configurations, but others may not. Sensitivity of sybody binding to several recently identified RBD mutants is consistent with these structures.

scholarly journals Comparative Genomics of Receptor Binding Domains of Spike Protein and Receptor Interaction in COVID-19 Patient

2020 ◽  
Author(s):  
Rimjhim Dasgupta
Keyword(s):  
Receptor Binding ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Interaction ◽  
Receptor Binding Domain ◽  
Furin Cleavage ◽  
S Protein ◽  
Human Coronaviruses ◽  
Novel Coronavirus ◽  
Bat Coronavirus

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV, as determined by sequencing the viral RNA genome. Among its genome, S protein is surface-exposed and mediates entry into host cells. Currently it is one of the main targets for designing antibodies (Abs), therapeutic and vaccine. Earlier studies stated that ACE2 (angiotensin converting enzyme 2) could facilitate S protein mediated entry for this newly emerged coronavirus. Here we have taken an attempt to compare the genetic structure of receptor binding domain within S protein of highly pathogenic human coronaviruses (special reference to 2019-nCoV) with Bat coronavirus RaTG13. We have compared 2019-nCov receptor binding domain (RBD) with other pathogenic human coronaviruses (MERS-CoV and SARS-CoV) and Bat coronavirus RaTG13. We found that it is closest to RaTG13 RBD than MERS-CoV and SARS-CoV. Our study shows that 2019-nCov RBD also has significant identity with pangolin S protein RBD. We have also predicted the amino acid residues within RDB those may play important role for ACE2 receptor interaction. We identified unique signature for furin cleavage in 2019-nCov S protein but not in of other pathogenic human coronaviruses (tested here), bat coronavirus RaTG13 or pangolin.

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