Glimpses into evolutionary trajectories of SARS-CoV-2: emerging variants and potential immune evasion routes.
Ontology highlight
ABSTRACT:
SUBMITTER: Anastassopoulou C
PROVIDER: S-EPMC8111931 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
| S-EPMC8291755 | biostudies-literature
Project description:The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.
| S-EPMC9240077 | biostudies-literature
Project description:Immune checkpoint blockade therapies (ICBTs) targeting programmed cell death 1 (PD-1) and its ligand programmed death ligand-1 (PD-L1/B7-H1/CD274) have exhibited momentous clinical benefits and durable responses in multiple tumor types. However, primary resistance is found in considerable number of cancer patients, and most responders eventually develop acquired resistance to ICBT. To tackle these challenges, it is essential to understand how PD-L1 is controlled by cancer cells to evade immune surveillance. Recent research has shed new light into the mechanisms of PD-L1 regulation at genetic, epigenetic, transcriptional, translational, and posttranslational levels. In this work, we systematically discuss the mechanisms that control the gene amplification, epigenetic alteration, transcription, subcellular transportation and posttranscriptional modification of PD-L1 in cancer cells. We further categorize posttranscriptional PD-L1 regulations by the molecular modification of PD-L1, including glycosylation, phosphorylation, ubiquitination, deubiquitination, and lysosomal degradation. These findings may provide new routes for targeting tumor immune escape and catalyze the development of small molecular inhibitors of PD-L1 in addition to existing antibody drugs.
| S-EPMC5992436 | biostudies-literature
Project description:Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains in the COVID-19 pandemic. We report here cryo-electron microscopy structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Amino acid substitutions in the B.1.1.7 protein increase both the accessibility of its receptor binding domain and the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement may account for the increased transmissibility. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, making it resistant to some potent neutralizing antibodies. These findings provide structural details on how SARS-CoV-2 has evolved to enhance viral fitness and immune evasion.
| S-EPMC9245151 | biostudies-literature
Project description:The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents significant social, economic and political challenges worldwide. SARS-CoV-2 has caused over 3.5 million deaths since late 2019. Mutations in the spike (S) glycoprotein are of particular concern because it harbours the domain which recognises the angiotensin-converting enzyme 2 (ACE2) receptor and is the target for neutralising antibodies. Mutations in the S protein may induce alterations in the surface spike structures, changing the conformational B-cell epitopes and leading to a potential reduction in vaccine efficacy. Here, we summarise how the more important variants of SARS-CoV-2, which include cluster 5, lineages B.1.1.7 (Alpha variant), B.1.351 (Beta), P.1 (B.1.1.28/Gamma), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota) and B.1.617.2 (Delta) confer mutations in their respective spike proteins which enhance viral fitness by improving binding affinity to the ACE2 receptor and lead to an increase in infectivity and transmission. We further discuss how these spike protein mutations provide resistance against immune responses, either acquired naturally or induced by vaccination. This information will be valuable in guiding the development of vaccines and other therapeutics for protection against the ongoing coronavirus disease 2019 (COVID-19) pandemic.
| S-EPMC8306177 | biostudies-literature
Project description:The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.
| S-EPMC8371089 | biostudies-literature
Project description:The recent global surge in COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely Alpha, Beta, Gamma, Delta, etc. The molecular mechanism underlying such surge is elusive due to 4,653 non-degenerate mutations on the spike protein, which is the target of most COVID-19 vaccines. The understanding of the molecular mechanism of transmission and evolution is a prerequisite to foresee the trend of emerging vaccine-breakthrough variants and the design of mutation-proof vaccines and monoclonal antibodies. We integrate the genotyping of 1,489,884 SARS-CoV-2 genomes isolates, 130 human antibodies, tens of thousands of mutational data points, topological data analysis, and deep learning to reveal SARS-CoV-2 evolution mechanism and forecast emerging vaccine-escape variants. We show that infectivity-strengthening and antibody-disruptive co-mutations on the S protein RBD can quantitatively explain the infectivity and virulence of all prevailing variants. We demonstrate that Lambda is as infectious as Delta but is more vaccine-resistant. We analyze emerging vaccine-breakthrough co-mutations in 20 countries, including the United Kingdom, the United States, Denmark, Brazil, and Germany, etc. We envision that natural selection through infectivity will continue to be the main mechanism for viral evolution among unvaccinated populations, while antibody disruptive co-mutations will fuel the future growth of vaccine-breakthrough variants among fully vaccinated populations. Finally, we have identified the co-mutations that have the great likelihood of becoming dominant: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. We predict they, particularly the last four, will break through existing vaccines. We foresee an urgent need to develop new vaccines that target these co-mutations.
| S-EPMC8437313 | biostudies-literature
Project description:The worldwide outbreak of SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 as a novel human coronavirus, was the worrying news at the beginning of 2020. Since its emergence complicated more than 870,000 individuals and led to more than 43,000 deaths worldwide. Considering to the potential threat of a pandemic and transmission severity of it, there is an urgent need to evaluate and realize this new virus's structure and behavior and the immunopathology of this disease to find potential therapeutic protocols and to design and develop effective vaccines. This disease is able to agitate the response of the immune system in the infected patients, so ARDS, as a common consequence of immunopathological events for infections with Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2, could be the main reason for death. Here, we summarized the immune response and immune evasion characteristics in SARS-CoV, MERS-CoV, and SARS-CoV-2 and therapeutic and prophylactic strategies with a focus on vaccine development and its challenges.
| S-EPMC7522676 | biostudies-literature
Project description:The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.
| S-EPMC7986999 | biostudies-literature
Project description:There is an urgent need to understand the functional effects of mutations in emerging variants of SARS-CoV-2. Variants of concern (alpha, beta, gamma and delta) acquired four patterns of spike glycoprotein mutations that enhance transmissibility and immune evasion: 1) mutations in the N-terminal domain (NTD), 2) mutations in the Receptor Binding Domain (RBD), 3) mutations at interchain contacts of the spike trimer, and 4) furin cleavage site mutations. Most distinguishing mutations among variants of concern are exhibited in the NTD, localized to sites of high structural flexibility. Emerging variants of interest such as mu, lambda and C.1.2 exhibit the same patterns of mutations as variants of concern. There is a strong likelihood that SARS-CoV-2 variants will continue to emerge with mutations in these defined patterns, thus providing a basis for the development of next line antiviral drugs and vaccine candidates.
| S-EPMC8606318 | biostudies-literature