scholarly journals The Spike of Concern—The Novel Variants of SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1002
Author(s):  
Anna Winger ◽  
Thomas Caspari
Keyword(s):  
Binding Activity ◽  
Neutralising Antibodies ◽  
High Sequence Identity ◽  
Allosteric Control ◽  
Viral Spread ◽  
Surface Areas ◽  
The United Kingdom ◽  
Angiotensin I Converting Enzyme ◽  
Novel Variants ◽  
Key Sites

The high sequence identity of the first SARS-CoV-2 samples collected in December 2019 at Wuhan did not foretell the emergence of novel variants in the United Kingdom, North and South America, India, or South Africa that drive the current waves of the pandemic. The viral spike receptor possesses two surface areas of high mutagenic plasticity: the supersite in its N-terminal domain (NTD) that is recognised by all anti-NTD antibodies and its receptor binding domain (RBD) where 17 residues make contact with the human Ace2 protein (angiotensin I converting enzyme 2) and many neutralising antibodies bind. While NTD mutations appear at first glance very diverse, they converge on the structure of the supersite. The mutations within the RBD, on the other hand, hone in on only a small number of key sites (K417, L452, E484, N501) that are allosteric control points enabling spike to escape neutralising antibodies while maintaining or even gaining Ace2-binding activity. The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open spike protomers in the homo-trimeric receptor complex. This review discusses the recent spike mutations as well as their evolution.

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

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.

COVID-19: Adapting to change, general surgery at a district general hospital in the United Kingdom

2019 ◽  
Vol 30 (10) ◽  
pp. 301-308
Author(s):  
Sonia Ike ◽  
Chijioke Ikechi ◽  
Jaideep Rait ◽  
Ankur Shah
Keyword(s):  
United Kingdom ◽  
General Hospital ◽  
General Surgery ◽  
Major Change ◽  
Holistic Approach ◽  
District General Hospital ◽  
Viral Spread ◽  
The United Kingdom ◽  
Staff Wellbeing ◽  
Surgery Department

The Coronavirus pandemic has caused major change across the world and in the National Health Service. In order to cope and help limit contagion, numerous institutions recognised the need to adjust clinical practice quickly yet safely. In this paper, we aim to describe the changes implemented in a general surgery department at a district general hospital in the United Kingdom. Across the surgical specialties, frameworks, protocols and guidelines have been established locally and nationally. The aerosol generating procedures involved in general surgery required us to alter our daily activities. Modifications to patient management were necessary to try and reduce viral spread. Staff wellbeing was heavily promoted in order to help maintain the frontline workforce. A holistic approach was required.

scholarly journals SARS-CoV-2 neutralising antibodies in Dogs and Cats in the United Kingdom

2021 ◽  
Author(s):  
Shirley Smith ◽  
Enyia Anderson ◽  
Cintia Cansado Utrilla ◽  
Tessa Prince ◽  
Sean Farrell ◽  
...  
Keyword(s):  
United Kingdom ◽  
Large Scale ◽  
Companion Animals ◽  
Human Infection ◽  
Neutralising Antibodies ◽  
Diagnostic Laboratory ◽  
The United Kingdom ◽  
The Uk ◽  
Human Infections ◽  
Second Wave

Companion animals are susceptible to SARS-CoV-2 infection and sporadic cases of pet infections have occurred in the United Kingdom. Here we present the first large-scale serological survey of SARS-CoV-2 neutralising antibodies in dogs and cats in the UK. Results are reported for 688 sera (454 canine, 234 feline) collected by a large veterinary diagnostic laboratory for routine haematology during three time periods; pre-COVID-19 (January 2020), during the first wave of UK human infections (April-May 2020) and during the second wave of UK human infections (September 2020-February 2021). Both pre-COVID-19 sera and those from the first wave tested negative. However, in sera collected during the second wave, 1.4% (n=4) of dogs and 2.2% (n=2) cats tested positive for neutralising antibodies. The low numbers of animals testing positive suggests pet animals are unlikely to be a major reservoir for human infection in the UK. However, continued surveillance of in-contact susceptible animals should be performed as part of ongoing population health surveillance initiatives.

scholarly journals SARS-CoV-2 neutralising antibodies in dogs and cats in the United Kingdom

2021 ◽  
pp. 100011
Author(s):  
Shirley L. Smith ◽  
Enyia R. Anderson ◽  
Cintia Cansado-Utrilla ◽  
Tessa Prince ◽  
Sean Farrell ◽  
...  
Keyword(s):  
United Kingdom ◽  
Neutralising Antibodies ◽  
The United Kingdom

scholarly journals SARS-CoV-2 European resurgence foretold: interplay of introductions and persistence by leveraging genomic and mobility data

2021 ◽  
Author(s):  
Philippe Lemey ◽  
Nick Ruktanonchai ◽  
Samuel Hong ◽  
Vittoria Colizza ◽  
Chiara Poletto ◽  
...  
Keyword(s):  
United Kingdom ◽  
Late Summer ◽  
Epidemiological Data ◽  
European Countries ◽  
Cross Border ◽  
Mobility Data ◽  
The United Kingdom ◽  
Intervention Measures ◽  
Novel Variants ◽  
Second Wave

Abstract Following the first wave of SARS-CoV-2 infections in spring 2020, Europe experienced a resurgence of the virus starting late summer that was deadlier and more difficult to contain. Relaxed intervention measures and summer travel have been implicated as drivers of the second wave. Here, we build a phylogeographic model to evaluate how newly introduced lineages, as opposed to the rekindling of persistent lineages, contributed to the COVID-19 resurgence in Europe. We inform this model using genomic, mobility and epidemiological data from 10 West European countries and estimate that in many countries more than 50% of the lineages circulating in late summer resulted from new introductions since June 15th. The success in onwards transmission of these lineages is predicted by SARS-CoV-2 incidence during this period. Relatively early introductions from Spain into the United Kingdom contributed to the successful spread of the 20A.EU1/B.1.177 variant. The pervasive spread of variants that have not been associated with an advantage in transmissibility highlights the threat of novel variants of concern that emerged more recently and have been disseminated by holiday travel. Our findings indicate that more effective and coordinated measures are required to contain spread through cross-border travel.

scholarly journals Deep phylogenetic-based clustering analysis uncovers new and shared mutations in SARS-CoV-2 variants as a result of directional and convergent evolution

2021 ◽  
Author(s):  
Danilo Rosa Nunes ◽  
Carla Torres Braconi ◽  
Louisa Ludwig-Begall ◽  
Clarice Weis Arns ◽  
Luiz Mario Ramos Janini ◽  
...  
Keyword(s):  
Clustering Analysis ◽  
Rna Virus ◽  
Point Mutations ◽  
Linear Perspective ◽  
Global Public Health ◽  
Health Crisis ◽  
Viral Spread ◽  
Novel Variants ◽  
Directional Evolution ◽  
The Usa

Nearly two decades after the last epidemic caused by a severe acute respiratory syndrome coronavirus (SARS-CoV), newly emerged SARS-CoV-2 quickly spread in 2020 and precipitated an ongoing global public health crisis. Both the continuous accumulation of point mutations, owed to the naturally imposed genomic plasticity of SARS-CoV-2 evolutionary processes, as well as viral spread over time, allow this RNA virus to gain new genetic identities, spawn novel variants and enhance its potential for immune evasion. Here, through an in-depth phylogenetic clustering analysis of upwards of 200,000 whole-genome sequences, we reveal the presence of not previously reported and hitherto unidentified mutations and recombination breakpoints in Variants of Concern (VOC) and Variants of Interest (VOI) from Brazil, India (Beta, Eta and Kappa) and the USA (Beta, Eta and Lambda). Additionally, we identify sites with shared mutations under directional evolution in the SARS-CoV-2 Spike-encoding protein of VOC and VOI, tracing a heretofore-undescribed correlation with viral spread in South America, India and the USA. Our evidence-based analysis provides well-supported evidence of similar pathways of evolution for such mutations in all SARS-CoV-2 variants and sub-lineages. This raises two pivotal points: the co-circulation of variants and sub-lineages in close evolutionary environments, which sheds light onto their trajectories into convergent and directional evolution (i), and a linear perspective into the prospective vaccine efficacy against different SARS-CoV-2 strains (ii).

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

eLife ◽  
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.

scholarly journals Aurora kinase-induced phosphorylation excludes transcription factor RUNX from the chromatin to facilitate proper mitotic progression

2016 ◽  
Vol 113 (23) ◽  
pp. 6490-6495 ◽  
Author(s):  
Linda Shyue Huey Chuang ◽  
Jian Ming Khor ◽  
Soak Kuan Lai ◽  
Shubham Garg ◽  
Vaidehi Krishnan ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Aurora Kinase ◽  
Binding Activity ◽  
Mitotic Progression ◽  
Runt Domain ◽  
Mitotic Entry ◽  
Dna Binding Activity ◽  
Key Sites ◽  
Runx Proteins

The Runt-related transcription factors (RUNX) are master regulators of development and major players in tumorigenesis. Interestingly, unlike most transcription factors, RUNX proteins are detected on the mitotic chromatin and apparatus, suggesting that they are functionally active in mitosis. Here, we identify key sites of RUNX phosphorylation in mitosis. We show that the phosphorylation of threonine 173 (T173) residue within the Runt domain of RUNX3 disrupts RUNX DNA binding activity during mitotic entry to facilitate the recruitment of RUNX proteins to mitotic structures. Moreover, knockdown of RUNX3 delays mitotic entry. RUNX3 phosphorylation is therefore a regulatory mechanism for mitotic entry. Cancer-associated mutations of RUNX3 T173 and its equivalent in RUNX1 further corroborate the role of RUNX phosphorylation in regulating proper mitotic progression and genomic integrity.

scholarly journals CV2CoV, an enhanced mRNA-based SARS-CoV-2 vaccine candidate, supports higher protein expression and improved immunogenicity in rats

2021 ◽  
Author(s):  
Nicole Roth ◽  
Jacob Schoen ◽  
Donata Hoffmann ◽  
Moritz Thran ◽  
Andreas Thess ◽  
...  
Keyword(s):  
Cell Culture ◽  
Protein Expression ◽  
First Generation ◽  
Vaccine Candidate ◽  
Antibody Responses ◽  
Neutralising Antibodies ◽  
Vaccination Programs ◽  
Human Host ◽  
Novel Variants ◽  
Clinical Candidate

More than a year after emergence of the SARS-CoV-2 pandemic, multiple first-generation vaccines are approved and available for vaccination. Still, many challenges remain. The ongoing vaccination programs across the globe suffer from insufficient vaccine supply. The virus is adapting to the human host and novel variants are circulating that are neutralised less efficiently by antibodies raised against ancestral SARS-CoV-2 variants. Here, we describe CV2CoV, a second-generation mRNA vaccine developed for enhanced protein expression and immunogenicity. CV2CoV supports increased levels of protein expression in cell culture compared to our clinical candidate CVnCoV. Vaccination with CV2CoV induces high levels of virus neutralising antibodies with accelerated kinetics in rats. Robust antibody responses are reflected in significant cross-neutralisation of circulating SARS-CoV-2 variants of concern, i.e. B.1.1.7 and B.1.351. Together, these results underline the value of CV2CoV as next-generation SARS-CoV-2 mRNA vaccine

scholarly journals Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020

2020 ◽  
Vol 25 (42) ◽  
Author(s):  
Craig P Thompson ◽  
Nicholas E Grayson ◽  
Robert S Paton ◽  
Jai S Bolton ◽  
José Lourenço ◽  
...  
Keyword(s):  
United Kingdom ◽  
Severe Acute Respiratory Syndrome ◽  
Geographical Distribution ◽  
Blood Donors ◽  
Population Exposure ◽  
Serological Study ◽  
Neutralising Antibodies ◽  
Past Infection ◽  
The United Kingdom ◽  
Blood Banks

Background The progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression. Aim Our objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic. Methods A pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019. Results All samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5–6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic. Conclusion Although blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.

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