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

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.

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Omicron: The pandemic propagator and lockdown instigator – what can be learnt from South Africa and such discoveries in future

Nepal Journal of Epidemiology ◽

10.3126/nje.v11i4.41569 ◽

2021 ◽

Vol 11 (4) ◽

pp. 1126-1129

Author(s):

Indrajit Banerjee ◽

Jared Robinson ◽

Indraneel Banerjee ◽

Brijesh Sathian

Keyword(s):

South Africa ◽

United Kingdom ◽

South African ◽

Clinical Features ◽

Developing Nations ◽

Global Community ◽

The United Kingdom ◽

New Variant ◽

Predominant Variant ◽

Current Point

The SARS-CoV-2 virus which causes the disease termed COVID-19 ripped through the globe in the latter part of 2019 and has left a state of fear, death and destruction in its wake. The Omicron variant was officially announced by the South African authorities on the 24th of November 2021, with the first confirmed sample of the infection being collected on the 9th of November 2021. The initial cases were flagged as a possible new variant due to the stark differences in the presentation and clinical features of the patients. At the time of Omicron’s discovery, the predominant variant circulating within South Africa was the Delta variant B.1.617.2 which typically presented with more severe and stark symptoms. Omicron spread rapidly within the Southern African content and abroad, principally South Africa, Botswana, Hongkong and Israel were among the first countries to record cases of the new variant. The first European case of the Omicron variant was confirmed on the 26th of November 2021 in Belgium. Towards the end of November 2021 cases of the new variant had been confirmed and recorded in France, the United Kingdom, Germany, Portugal and Scotland. Additional cases of the Omicron variant have been confirmed in Canada and Australia. At this current point in the development of the Omicron upsurge in cases the international community should aim for further vaccinations among their fellow countrymen, but more so vaccine equality should be ensured. Such equality should be ensured in the developing nations as the virus does not respect any boundaries or territories and thus a higher level of vaccination worldwide will confer greater protection to the global community as a whole.

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Molecular docking and dynamic simulation of conserved B cell epitope of SARS-CoV-2 glycoprotein Indonesian isolates: an immunoinformatic approach

F1000Research ◽

10.12688/f1000research.54258.1 ◽

2021 ◽

Vol 10 ◽

pp. 813

Author(s):

Fedik Abdul Rantam ◽

Viol Dhea Kharisma ◽

Christrijogo Sumartono ◽

Jusak Nugraha ◽

Andi Yasmin Wijaya ◽

...

Keyword(s):

United States ◽

South Africa ◽

United Kingdom ◽

B Cell ◽

Vaccine Candidate ◽

The United States ◽

Spike Glycoprotein ◽

Mhc Ii ◽

Conserved Regions ◽

The United Kingdom

Background: An immunoinformatic approach may be useful to investigate the conserved region in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Indonesia isolates. The aim of this study was to investigate Indonesian SARS-CoV-2 isolates based on B cell epitopes by targeting the conserved regions in the spike glycoprotein to trigger increased multi-variant virus neutralization and memory response for the development of vaccine seed candidates. Methods: SARS-CoV-2 spike glycoprotein gene sequences originating from Indonesia were compared with Wuhan (China), the United Kingdom, South Africa, India, the United States, and Brazil isolates obtained from the NCBI and GISAID databases. The recognition of antigens was carried out directly using B cells through the B cell receptor (BCR). An indirect B cell activation by Cluster of Differentiation (CD)4+ T cells and major histocompatibility complex (MHC)-II was predicted through the binding with human leukocyte antigen (HLA) based on IC50 value. In addition, vaccine allergenicity and toxicity were investigated. During the molecular complex examination, the 3D peptide structure was investigated and the lowest amount of energy formed when the vaccine candidate peptide bound to BCR and MHC-II was calculated. Results: As a result, the spike glycoprotein sequences of Indonesian SARS-CoV-2 isolates had conserved regions which were very similar to reference countries such as China, the United Kingdom, South Africa, India, the United States, and Brazil. Conclusion: It was predicted that the conserved regions could be identified as the epitope of B and T CD4+ cells that produced the peptides for vaccine candidate with antigenic, non-allergen, and non-toxic properties.

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Neutralizing response against E484K variant after original SARS-CoV-2 infection

10.1101/2021.05.07.21256803 ◽

2021 ◽

Author(s):

Takuma Hayashi ◽

Nobuo Yaegashi ◽

Ikuo Konishi

Keyword(s):

South Africa ◽

United Kingdom ◽

Severe Acute Respiratory Syndrome ◽

The Body ◽

Proliferative Potential ◽

Spike Glycoprotein ◽

Highly Pathogenic ◽

The United Kingdom ◽

The Uk ◽

Neutralization Response

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variants, which are spreading in the United Kingdom (UK) and elsewhere, have been found in infected individuals in Japan. The virus mutates, to facilitate its life in the host, during the process of repeated proliferation in the body of the host, including humans. In other words, it is natural that a human-compatible mutant strain always predominates in infection and proliferation. As a result, the viral mutants acquire strong proliferative potential in the host and are highly pathogenic. The number of people infected with the mutated SARS-CoV-2 variant E484K, which is different from the SARS-CoV-2 variants that are spreading in the UK, South Africa, and Brazil, is increasing in Tokyo. It has been pointed out that the effects of immunity and vaccines may be reduced against the Tokyo-type SARS-CoV-2 variant E484K. We have investigated the neutralization response to various mutations in the spike glycoprotein using the serum of people already infected with the original SARS-CoV-2. The results showed that SARS-CoV-2 variants with Y543F or N501Y mutations in the spike glycoprotein affect the neutralization reaction. However, single E484K mutations within the spiked glycoprotein of the Tokyo-type SARS-CoV-2 variant are unlikely to have a significant effect on the affinity of the host antibody for the virus.

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Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains

eLife ◽

10.7554/elife.69317 ◽

2021 ◽

Vol 10 ◽

Author(s):

Nikhil Faulkner ◽

Kevin W Ng ◽

Mary Y Wu ◽

Ruth Harvey ◽

Marios Margaritis ◽

...

Keyword(s):

South Africa ◽

United Kingdom ◽

Severe Acute Respiratory Syndrome ◽

Parental Strain ◽

Cross Reactivity ◽

Major Determinant ◽

Spike Glycoprotein ◽

Neutralising Antibodies ◽

The United Kingdom ◽

Vaccination Campaigns

Background: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood.Methods: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity.Results: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection.Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric.

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SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants from United Kingdom and South Africa

Research Ideas and Outcomes ◽

10.3897/rio.7.e62936 ◽

2021 ◽

Vol 7 ◽

Author(s):

Victor Padilla-Sanchez

Keyword(s):

South Africa ◽

United Kingdom ◽

Structural Analysis ◽

Receptor Binding ◽

Binding Domain ◽

The Other ◽

Receptor Binding Domain ◽

Converting Enzyme ◽

Spike Glycoprotein ◽

Angiotensin Converting Enzyme 2

SARS-CoV-2 has caused more than 80 million infections and close to 2 million deaths worldwide as of January 2021. This pandemic has caused an incredible damage to humanity being it medically and/or financially halting life as we know it. If it were not enough, the current virus is changing to a more deadly form because of the mutations that are arising on its genome. Importantly, two variants have emerged in recent months, one in United Kingdom and the other in South Africa that are more infectious and escape antibody binding. These two variants have mutations in the receptor binding domain of the spike glycoprotein namely N501Y (UK, SA), K417N (SA) and E484K (SA). Here, I present a structural analysis of spike glycoprotein bound to ACE2 (angiotensin converting enzyme 2) where the mutations have been introduced in silico showing the reason why these variants bind better to ACE2 receptors.

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RIC in COVID-19—a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-021-07221-y ◽

2021 ◽

Author(s):

Sean M. Davidson ◽

Kishal Lukhna ◽

Diana A. Gorog ◽

Alan D. Salama ◽

Alejandro Rosell Castillo ◽

...

Keyword(s):

South Africa ◽

Clinical Trial ◽

United Kingdom ◽

Inflammatory Cytokines ◽

In Vitro Cytotoxicity ◽

Cytokine Storm ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning ◽

The United Kingdom

Abstract Purpose Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. “RIC in COVID-19” is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. Methods A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. Conclusions The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. Trial Registration NCT04699227, registered January 7th, 2021.

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Isolation and characterization of the new SARS-CoV-2 variant in travellers from the United Kingdom to India: VUI-202012/01 of the B.1.1.7 lineage

Journal of Travel Medicine ◽

10.1093/jtm/taab009 ◽

2021 ◽

Vol 28 (2) ◽

Cited By ~ 1

Author(s):

Pragya D Yadav ◽

Dimpal A Nyayanit ◽

Rima R Sahay ◽

Prasad Sarkale ◽

Jayshri Pethani ◽

...

Keyword(s):

United Kingdom ◽

Severe Acute Respiratory Syndrome ◽

Surveillance System ◽

The United Kingdom ◽

Isolation And Characterization ◽

New Variant ◽

The Uk ◽

Local Transmission

We have isolated the new severe acute respiratory syndrome coronavirus-2 variant of concern 202 012/01 from the positive coronavirus disease 2019 cases that travelled from the UK to India in the month of December 2020. This emphasizes the need for the strengthened surveillance system to limit the local transmission of this new variant.

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A cross-sectional survey assessing the influence of theoretically informed behavioural factors on hand hygiene across seven countries during the COVID-19 pandemic

BMC Public Health ◽

10.1186/s12889-021-11491-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

K. A. Schmidtke ◽

K. G. Drinkwater

Keyword(s):

South Africa ◽

Saudi Arabia ◽

United Kingdom ◽

Hand Hygiene ◽

Behaviour Change ◽

Surface Cleaning ◽

Behaviour Change Techniques ◽

Cross Sectional ◽

Surface Areas ◽

The United Kingdom

Abstract Background Human hygiene behaviours influence the transmission of infectious diseases. Changing maladaptive hygiene habits has the potential to improve public health. Parents and teachers can play an important role in disinfecting surface areas and in helping children develop healthful handwashing habits. The current study aims to inform a future intervention that will help parents and teachers take up this role using a theoretically and empirically informed behaviour change model called the Capabilities-Opportunities-Motivations-Behaviour (COM-B) model. Methods A cross-sectional online survey was designed to measure participants’ capabilities, opportunities, and motivations to [1] increase their children’s handwashing with soap and [2] increase their cleaning of surface areas. Additional items captured how often participants believed their children washed their hands. The final survey was administered early in the coronavirus pandemic (May and June 2020) to 3975 participants from Australia, China, India, Indonesia, Saudi Arabia, South Africa, and the United Kingdom. Participants self-identified as mums, dads, or teachers of children 5 to 10 years old. ANOVAs analyses were used to compare participant capabilities, opportunities, and motivations across countries for handwashing and surface disinfecting. Multiple regressions analyses were conducted for each country to assess the predictive relationship between the COM-B components and children’s handwashing. Results The ANOVA analyses revealed that India had the lowest levels of capability, opportunity, and motivation, for both hand hygiene and surface cleaning. The regression analyses revealed that for Australia, Indonesia, and South Africa, the capability component was the only significant predictor of children’s handwashing. For India, capability and opportunity were significant. For the United Kingdom, capability and motivation were significant. Lastly, for Saudi Arabia all components were significant. Conclusions The discussion explores how the Behaviour Change Wheel methodology could be used to guide further intervention development with community stakeholders in each country. Of the countries assessed, India offers the greatest room for improvement, and behaviour change techniques that influence people’s capability and opportunities should be prioritised there.

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