scholarly journals Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine–elicited human sera

Science ◽  
2021 ◽  
pp. eabg6105 ◽  
Author(s):  
Alexander Muik ◽  
Ann-Kathrin Wallisch ◽  
Bianca Sänger ◽  
Kena A. Swanson ◽  
Julia Mühl ◽  
...  
Keyword(s):  
United Kingdom ◽  
Amino Acid ◽  
Neutralizing Antibodies ◽  
Reference Strain ◽  
Spike Protein ◽  
The United Kingdom ◽  
Human Sera

Recently, a new SARS-CoV-2 lineage called B.1.1.7 (variant of concern: VOC 202012/01) emerged in the United Kingdom that was reported to spread more efficiently and faster than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we tested SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 40 participants who were vaccinated in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had slightly reduced but overall largely preserved neutralizing titers against the B.1.1.7 lineage pseudovirus. These data indicate that the B.1.1.7 lineage will not escape BNT162b2-mediated protection.

scholarly journals Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera

2021 ◽  
Author(s):  
Alexander Muik ◽  
Ann-Kathrin Wallisch ◽  
Bianca Sänger ◽  
Kena A. Swanson ◽  
Julia Mühl ◽  
...  
Keyword(s):  
United Kingdom ◽  
Amino Acid ◽  
Neutralizing Antibodies ◽  
Reference Strain ◽  
Spike Protein ◽  
The United Kingdom ◽  
Human Sera

AbstractRecently, a new SARS-CoV-2 lineage called B.1.1.7 has emerged in the United Kingdom that was reported to spread more efficiently than other strains. This variant has an unusually large number of mutations with 10 amino acid changes in the spike protein, raising concerns that its recognition by neutralizing antibodies may be affected. Here, we investigated SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 16 participants in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection.

scholarly journals Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

2020 ◽  
Author(s):  
Kathy Leung ◽  
Marcus HH Shum ◽  
Gabriel M Leung ◽  
Tommy TY Lam ◽  
Joseph T Wu
Keyword(s):  
United Kingdom ◽  
Amino Acid ◽  
Receptor Binding ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Deletion ◽  
The United Kingdom ◽  
Mutant Strains ◽  
The Uk

AbstractTwo new SARS-CoV-2 lineages with the N501Y mutation in the receptor binding domain of the spike protein have rapidly become prevalent in the UK. We estimated that the earlier 501Y lineage without amino acid deletion Δ69/Δ70 circulating mainly between early September to mid-November was 10% (6-13%) more transmissible than the 501N lineage, and the currently dominant 501Y lineage with amino acid deletion Δ69/Δ70 circulating since late September was 75% (70-80%) more transmissible than the 501N lineage.

scholarly journals Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Kathy Leung ◽  
Marcus HH Shum ◽  
Gabriel M Leung ◽  
Tommy TY Lam ◽  
Joseph T Wu
Keyword(s):  
United Kingdom ◽  
Amino Acid ◽  
Receptor Binding ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Deletion ◽  
The United Kingdom ◽  
Mutant Strains

Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor-binding domain of the spike protein spread rapidly in the United Kingdom. We estimated that the earlier 501Y lineage without amino acid deletion Δ69/Δ70, circulating mainly between early September and mid-November, was 10% (6–13%) more transmissible than the 501N lineage, and the 501Y lineage with amino acid deletion Δ69/Δ70, circulating since late September, was 75% (70–80%) more transmissible than the 501N lineage.

scholarly journals In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2–Spike RBD Interface

2021 ◽  
Vol 22 (4) ◽  
pp. 1695
Author(s):  
Bruno O. Villoutreix ◽  
Vincent Calvez ◽  
Anne-Geneviève Marcelin ◽  
Abdel-Majid Khatib
Keyword(s):  
Amino Acid ◽  
South African ◽  
In Silico ◽  
Neutralizing Antibodies ◽  
Viral Escape ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
The South ◽  
African Strain ◽  
The Uk

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.

Construction and immunogenic studies of a mFc fusion receptor binding domain (RBD) of spike protein as a subunit vaccine against SARS-CoV-2 infection

2020 ◽  
Vol 56 (61) ◽  
pp. 8683-8686 ◽  
Author(s):  
Xiaoxiao Qi ◽  
Bixia Ke ◽  
Qian Feng ◽  
Deying Yang ◽  
Qinghai Lian ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fusion Protein ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Humoral And Cellular Immunity ◽  
A Subunit

Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice.

scholarly journals Structural analysis of the Spike of the Omicron SARS-COV-2 variant by Cryo-EM and implications for immune evasion

2021 ◽  
Author(s):  
Dongchun Ni ◽  
Kelvin Lau ◽  
Priscilla Turelli ◽  
Charlene Raclot ◽  
Bertrand Beckert ◽  
...  
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Structural Analysis ◽  
High Resolution ◽  
Immune Evasion ◽  
Spike Protein ◽  
Spike Glycoprotein ◽  
The United Kingdom ◽  
New Variant ◽  
Structural Insights

The Omicron (B.1.1.529) SARS-COV-2 was reported on November 24, 2021 and declared a variant of concern a couple of days later. With its constellation of mutations acquired by this variant on its Spike glycoprotein and the speed at which this new variant has replaced the previously dominant variant Delta in South Africa and the United Kingdom, it is crucial to have atomic structural insights to reveal the mechanism of its rapid proliferation. Here we present a high-resolution cryo-EM structure of the Spike protein of the Omicron variant.

scholarly journals An interactive COVID-19 virus Mutation Tracker (CovMT) with a particular focus on critical mutations in the Receptor Binding Domain (RBD) region of the Spike protein

2021 ◽  
Author(s):  
Intikhab Alam ◽  
Aleksandar Radovanovic ◽  
Roberto Incitti ◽  
Allan Kamau ◽  
Muhammad Alarawi ◽  
...  
Keyword(s):  
United Kingdom ◽  
Receptor Binding ◽  
Treatment Strategies ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Link Type ◽  
The United Kingdom ◽  
Public Resources ◽  
One Year

AbstractAlmost one year has passed since the appearance of SARS-CoV-2, causing the COVID-19 pandemic. The number of confirmed SARS-Cov-2 cases worldwide has now reached ∼92 million, with 2 million reported deaths (https://covid19.who.int). Nearly 400,000 SARS-Cov-2 genomes were sequenced from COVID-19 samples and added to public resources such as GISAID (https://gisaid.org). With the vaccines becoming available or entering trials (https://covid19.trackvaccines.org), it is vital to keep track of mutations in the genome of SARS-CoV-2, especially in the Spike protein’s Receptor Binding Domain (RBD) region, which could have a potential impact on disease severity and treatment strategies.1–3 In the wake of a recent increase in cases with a potentially more infective RBD mutation (N501Y) in the United Kingdom, countries worldwide are concerned about the spread of this or similar variants. Impressive sampling and timely increase in sequencing efforts related to COVID-19 in the United Kingdom (UK) helped detect and monitor the spread of the new N501Y variant. Similar sequencing efforts are needed in other countries for timely tracking of this or different variants. To track geographic sequencing efforts and mutations, with a particular focus on RBD region of the Spike protein, we present our daily updated COVID-19 virus Mutation Tracker system, see https://www.cbrc.kaust.edu.sa/covmt.

scholarly journals Importance of mutations in amino acid 484 of the Spike protein of SARS-CoV-2: rapid detection by restriction enzyme analysis

2021 ◽  
Vol 62 ◽  
pp. 18-26
Author(s):  
Rossana C Jaspe ◽  
Yoneira Sulbarn ◽  
Carmen L Loureiro ◽  
Pierina D´Angelo ◽  
Lieska Rodríguez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Restriction Enzyme ◽  
Rapid Detection ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Enzyme Analysis ◽  
Restriction Enzyme Analysis ◽  
Spike Gene ◽  
Detection Of Mutations ◽  
Viral Isolates

Variants of Concern of SARS-CoV-2 (VOCs), the new coronavirus responsible for COVID-19, have emerged in several countries. Mutations in the amino acid 484 of the Spike protein are particularly important and associated with some of these variants: E484K or E484Q. These mutations have been associated with evasion to neutralizing antibodies. Restriction enzyme analysis is proposed as a rapid method to detect these mutations. A search on GISAID was performed in April 2021 to detect the frequency of these two mutations in the sequence available and their association with other lineages. E484K, present in some VOCs, has emerged in several other lineages and is frequently found in recent viral isolates. A small amplicon from the Spike gene was digested with two enzymes: HpyAV, and MseI. The use of these two enzymes allows the detection of mutations at position 484, and to differentiate between these three conditions: non-mutated, and the presence of E484K or E484Q. A 100% correlation was observed with sequencing results. The proposed methodology, which allows for the screening of a great number of samples, will probably help to provide more information on the prevalence and epidemiology of these mutations worldwide, to select the candidates for whole-genome sequencing.

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