Dataset Information

Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries.

ABSTRACT: Recently, the SARS-CoV-2 variants from the United Kingdom (UK), South Africa, and Brazil have received much attention for their increased infectivity, potentially high virulence, and possible threats to existing vaccines and antibody therapies. The question remains if there are other more infectious variants transmitted around the world. We carry out a large-scale study of 506,768 SARS-CoV-2 genome isolates from patients to identify many other rapidly growing mutations on the spike (S) protein receptor-binding domain (RBD). We reveal that essentially all 100 most observed mutations strengthen the binding between the RBD and the host angiotensin-converting enzyme 2 (ACE2), indicating the virus evolves toward more infectious variants. In particular, we discover new fast-growing RBD mutations N439K, S477N, S477R, and N501T that also enhance the RBD and ACE2 binding. We further unveil that mutation N501Y involved in United Kingdom (UK), South Africa, and Brazil variants may moderately weaken the binding between the RBD and many known antibodies, while mutations E484K and K417N found in South Africa and Brazilian variants, L452R and E484Q found in India variants, can potentially disrupt the binding between the RBD and many known antibodies. Among these RBD mutations, L452R is also now known as part of the California variant B.1.427. Finally, we hypothesize that RBD mutations that can simultaneously make SARS-CoV-2 more infectious and disrupt the existing antibodies, called vaccine escape mutations, will pose an imminent threat to the current crop of vaccines. A list of most likely vaccine escape mutations is given, including S494P, Q493L, K417N, F490S, F486L, R403K, E484K, L452R, K417T, F490L, E484Q, and A475S. Mutation T478K appears to make the Mexico variant B.1.1.222 the most infectious one. Our comprehensive genetic analysis and protein-protein binding study show that the genetic evolution of SARS-CoV-2 on the RBD, which may be regulated by host gene editing, viral proofreading, random genetic drift, and natural selection, gives rise to more infectious variants that will potentially compromise existing vaccines and antibody therapies.

SUBMITTER: Wang R

PROVIDER: S-EPMC8123493 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPertussis and seasonal influenza are responsible for significant maternal, neonatal, and infant morbidity and mortality, but vaccine coverage rates (VCR) for both pertussis (administered as a tetanus, diphtheria, acellular pertussis [Tdap] vaccination) and seasonal influenza in pregnancy remain generally low. Only a small number of countries, including Spain, the United Kingdom (UK), and the United States (US), have high Tdap and seasonal influenza VCRs in pregnancy. The purpose of this study was to identify the key factors that contributed to the high VCRs observed in these countries.MethodsThe experience from both Tdap and seasonal influenza vaccination programmes during pregnancy were documented in Spain, the UK, and the US using a three-step approach. A literature review yielded 157 publications, and a further 117 documents were selected through desk research. A published five-pillar VCR framework for influenza was amended to evaluate the specific contributing factors leading to high Tdap and seasonal influenza VCRs among pregnant women.ResultsThe analysis identified components that contributed to higher VCR in pregnant women across three different healthcare systems in Spain, UK, and US. The combination of several key interventions in each country led to a rapid increase in VCR that reached near-optimal levels (i.e. 75% for seasonal influenza) within a few years. As well as inclusion in national immunisation programme and vaccine reimbursement, key components that were identified included the mobilisation of health authorities, prenatal care Healthcare Professionals (HCP) and scientific societies, the inclusion of vaccination in antenatal medical guidance, the provision of educational material to HCPs, and a strong disease awareness driven by recent pertussis outbreaks in each country.ConclusionsAlthough there is no simple, universal solution to improving sub-optimal VCRs, the list of components identified in this study from three countries with high-performing Tdap and seasonal influenza vaccination programmes provides a basis for public health and medical stakeholders in other countries to define strategies to successfully implement national vaccination programmes for pregnant women.

Project description:The relevance of race and ethnicity to genetics and medicine has long been a matter of debate. An emerging consensus holds that race and ethnicity are social constructs and thus poor proxies for genetic diversity. The goal of this study was to evaluate the relationship between race, ethnicity, and clinically relevant pharmacogenomic variation in cosmopolitan populations. We studied racially and ethnically diverse cohorts of 65,120 participants from the United States All of Us Research Program (All of Us) and 31,396 participants from the United Kingdom Biobank (UKB). Genome-wide patterns of pharmacogenomic variation-6311 drug response-associated variants for All of Us and 5966 variants for UKB-were analyzed with machine learning classifiers to predict participants' self-identified race and ethnicity. Pharmacogenomic variation predicts race/ethnicity with averages of 92.1% accuracy for All of Us and 94.3% accuracy for UKB. Group-specific prediction accuracies range from 99.0% for the White group in UKB to 92.9% for the Hispanic group in All of Us. Prediction accuracies are substantially lower for individuals who identified with more than one group in All of Us (16.7%) or as Mixed in UKB (70.7%). There are numerous individual pharmacogenomic variants with large allele frequency differences between race/ethnicity groups in both cohorts. Frequency differences for toxicity-associated variants predict hundreds of adverse drug reactions per 1000 treated participants for minority groups in All of Us. Our results indicate that race and ethnicity can be used to stratify pharmacogenomic risk in the US and UK populations and should not be discounted when making treatment decisions. We resolve the contradiction between the results reported here and the orthodoxy of race and ethnicity as non-genetic, social constructs by emphasizing the distinction between global and local patterns of human genetic diversity, and we stress the current and future limitations of race and ethnicity as proxies for pharmacogenomic variation.

Dataset Information

Vaccine-escape and fast-growing mutations in the United Kingdom, the United States, Singapore, Spain, India, and other COVID-19-devastated countries.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets