scholarly journals Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1192
Author(s):  
Ivana Lazarevic ◽  
Vera Pravica ◽  
Danijela Miljanovic ◽  
Maja Cupic
Keyword(s):  
Immune Evasion ◽  
Human Population ◽  
Evolutionary Rate ◽  
Spike Protein ◽  
Close Monitoring ◽  
Global Level ◽  
Therapeutic Application ◽  
Neutralization Capacity ◽  
Rapid Transmission ◽  
Potential Impact

Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during the COVID-19 pandemic has enabled it to acquire significant genetic diversity since it first entered the human population. This led to the emergence of numerous variants, some of them recently being labeled “variants of concern” (VOC), due to their potential impact on transmission, morbidity/mortality, and the evasion of neutralization by antibodies elicited by infection, vaccination, or therapeutic application. The potential to evade neutralization is the result of diversity of the target epitopes generated by the accumulation of mutations in the spike protein. While three globally recognized VOCs (Alpha or B.1.1.7, Beta or B.1.351, and Gamma or P.1) remain sensitive to neutralization albeit at reduced levels by the sera of convalescent individuals and recipients of several anti-COVID19 vaccines, the effect of spike variability is much more evident on the neutralization capacity of monoclonal antibodies. The newly recognized VOC Delta or lineage B.1.617.2, as well as locally accepted VOCs (Epsilon or B.1.427/29-US and B1.1.7 with the E484K-UK) are indicating the necessity of close monitoring of new variants on a global level. The VOCs characteristics, their mutational patterns, and the role mutations play in immune evasion are summarized in this review.

scholarly journals Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229e

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kathryn E Kistler ◽  
Trevor Bedford
Keyword(s):  
Adaptive Evolution ◽  
Immune Evasion ◽  
Human Population ◽  
Seasonal Influenza ◽  
Respiratory Infections ◽  
Antigenic Drift ◽  
Spike Protein ◽  
Immune Memory ◽  
Receptor Binding Domain ◽  
Genetic Changes

Seasonal coronaviruses (OC43, 229E, NL63, and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.

scholarly journals SARS-CoV-2: Genetic variability, mutations and variants of concern for the global world

2021 ◽  
Vol 72 (3) ◽  
pp. 1-7
Author(s):  
Maja Ćupić
Keyword(s):  
Human Population ◽  
Respiratory Infections ◽  
Cell Receptor ◽  
Close Monitoring ◽  
The Novel ◽  
Clinical Tests ◽  
Rapid Transmission ◽  
Novel Coronavirus ◽  
Global World ◽  
First Time

Since emerging from Wuhan, China, in December of 2019, the novel coronavirus named SARS-CoV-2 has been causing devastating severe respiratory infections in human population worldwide. The new emerging disease was called COVID-19 and, as early as the beginning of 2020, the world found itself in a COVID 19 pandemic. Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during the COVID-19 pandemic has enabled it to acquire significant genetic diversity since it first entered the human population. This led to the emergence of numerous variants, some of them recently being labeled, "variants of concern" (VOC). Emerging SARS-CoV-2 variants can be problematic if one or more of the independent mutations result in changes that make the virus more pathogenic, resistant to treatment, able to escape vaccines, or able to evade diagnostic tests. So far, four VOCs have been globally recognized (Alpha or B.1.1.7, Beta or B.1.351, Gamma or P.1 and newly recognized as VOC Delta or lineage B.1.617.2), and areas of the emerging variant of concern first time observed are United Kingdom, South Africa, Brazil, and India, respectively. Notable variants are those that contain mutations within the S gene, particularly within the region that codes for the receptor-binding domain (RBD) that recognize and attach the specific ACE2 cell receptor. These mutations are responsible for increased viral transmission and influence disease severity, reliability of clinical tests as well as vaccine and therapy efficacy. The characteristics of VOCs and their mutational patterns indicate the necessity of permanent close monitoring on a global level.

scholarly journals Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil

2021 ◽  
Author(s):  
Nuno R. Faria ◽  
Thomas A. Mellan ◽  
Charles Whittaker ◽  
Ingra M. Claro ◽  
Darlan da S. Candido ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Genome Sequencing ◽  
Immune Evasion ◽  
Protective Immunity ◽  
Spike Protein ◽  
Mortality Data ◽  
Previous Infection ◽  
Clock Analysis ◽  
Rapid Transmission ◽  
Molecular Clock Analysis

AbstractCases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4–2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.One-Sentence SummaryWe report the evolution and emergence of a SARS-CoV-2 lineage of concern associated with rapid transmission in Manaus.

scholarly journals Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses

2020 ◽  
Author(s):  
Kathryn E. Kistler ◽  
Trevor Bedford
Keyword(s):  
Adaptive Evolution ◽  
Immune Evasion ◽  
Human Population ◽  
Seasonal Influenza ◽  
Respiratory Infections ◽  
Antigenic Drift ◽  
Spike Protein ◽  
Immune Memory ◽  
Receptor Binding Domain ◽  
Genetic Changes

AbstractSeasonal coronaviruses (OC43, 229E, NL63 and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here, we address the influence of antigenic drift on immune evasion of seasonal coronaviruses. We provide evidence that at least two of these viruses, OC43 and 229E, are undergoing adaptive evolution in regions of the viral spike protein that are exposed to human humoral immunity. This suggests that reinfection may be due, in part, to positively-selected genetic changes in these viruses that enable them to escape recognition by the immune system. It is possible that, as with seasonal influenza, these adaptive changes in antigenic regions of the virus would necessitate continual reformulation of a vaccine made against them.

scholarly journals Subtle differences in the pathogenicity of SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in rhesus macaques

2021 ◽  
Author(s):  
Vincent Munster ◽  
Meaghan Flagg ◽  
Manmeet Singh ◽  
Brandi Williamson ◽  
Friederike Feldmann ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Human Population ◽  
Viral Antigen ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Spike Protein ◽  
Virus Shedding ◽  
Cytokines And Chemokines ◽  
Clade B ◽  
Medical Countermeasures

The emergence of several SARS-CoV-2 variants has caused global concerns about increased transmissibility, increased pathogenicity, and decreased efficacy of medical countermeasures. Animal models can be used to assess phenotypical changes in the absence of confounding factors that affect observed pathogenicity and transmissibility data in the human population. Here, we studied the pathogenicity of variants of concern (VOC) B.1.1.7 and B.1.351 in rhesus macaques and compared it to a recent clade B.1 SARS-CoV-2 isolate containing the D614G substitution in the spike protein. The B.1.1.7 VOC behaved similarly to the D614G with respect to clinical disease, virus shedding and virus replication in the respiratory tract. Inoculation with the B.1.351 isolate resulted in lower clinical scores in rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. We observed differences in the local innate immune response to infection. In bronchoalveolar lavages, cytokines and chemokines were upregulated on day 4 in animals inoculated with D614G and B.1.1.7 but not in those inoculated with B.1.351. In nasal samples, we did not detect upregulation of cytokines and chemokines in D614G or B.1.351-inoculated animals. However, cytokines and chemokines were upregulated in the noses of B.1.1.7-inoculated animals. Taken together, our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity.

scholarly journals Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Science ◽  
2021 ◽  
pp. eabh2644 ◽  
Author(s):  
Nuno R. Faria ◽  
Thomas A. Mellan ◽  
Charles Whittaker ◽  
Ingra M. Claro ◽  
Darlan da S. Candido ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Genome Sequencing ◽  
Immune Evasion ◽  
Molecular Clock ◽  
Spike Protein ◽  
Dynamical Model ◽  
Mortality Data ◽  
Clock Analysis ◽  
Protection Against Infection ◽  
Molecular Clock Analysis

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1, acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7–2.4-fold more transmissible, and that previous (non-P.1) infection provides 54–79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

scholarly journals ANALYSIS OF IMMUNE ESCAPE VARIANTS FROM ANTIBODY-BASED THERAPEUTICS AGAINST COVID-19.

2021 ◽  
Author(s):  
Daniele Focosi ◽  
Fabrizio Maggi ◽  
Massimo Franchini ◽  
Scott McConnell ◽  
Arturo Casadevall
Keyword(s):  
Public Health ◽  
Monoclonal Antibodies ◽  
Immune Evasion ◽  
Immune Escape ◽  
Selective Pressure ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Amino Acid Mutations

Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former is mainly associated with specific single amino acid mutations at residues within the receptor-binding domain (e.g., E484K/Q, Q493R, and S494P), the few cases of immune evasion after CCP were associated with recurrent deletions within the N-terminal domain of Spike protein (e.g, delHV69-70, delLGVY141-144 and delAL243-244). Continuous genomic monitoring of non-responders is needed to better understand immune escape frequencies and fitness of emerging variants.

scholarly journals Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity

2021 ◽  
pp. 101533
Author(s):  
Hylemariam Mihiretie Mengist ◽  
Arnaud John Kombe Kombe ◽  
Daniel Mekonnen ◽  
Abtie Abebaw ◽  
Melese Getachew ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Spike Protein ◽  
Induced Immunity

scholarly journals The Viral Zoonotic Diseases from bats

2020 ◽  
Vol 11 (11) ◽  
pp. 20876-20880
Author(s):  
Sheen Job ◽  
Megha Sharma ◽  
Dr Mahendra Singh
Keyword(s):  
Scientific Community ◽  
Vital Role ◽  
Zoonotic Diseases ◽  
Viral Dynamics ◽  
Emerging Pathogens ◽  
World Community ◽  
The World ◽  
Rapid Transmission ◽  
Potential Impact ◽  
The Impact

Bats are known reservoirs of virulent zoonotic pathogens not known to experience disease. They are known as nature’s pest controllers which are insectivorous and pollinators which are frugivorous in their nature. In the entire ecosystem bats play a vital role in various ways to sustain the diversity at its best. However, recent events have cast great aspersions on the bat behavior and the potential impact it has on Public Health not just in a specified region but  globally. The impact has been devastating and disastrous. The recent COVID 19 pandemic spell, opened the eyes of the scientific community, economists and even governments to work together. A host of issues were brought to light, as to how viral pathogenicity has played havoc with such virulence in the world community.  Numerous studies proved beyond doubt bats act as natural reservoirs for a large number of emerging and re emerging pathogens that other animals and humans can contract. It would be surprising to know that these viruses  are also listed in the bioterrorism list of pathogens. Such diversity shows that the bats are well adapted to the effects of virulent pathogens within their internal milieu. The first report of transmission of a bat virus to human was reported in 1960, it was the Rabies virus belonging to the Lyssa virus genus. SARS, Ebola, Nipah have already proven to be virulent and lethal.(1)   AIM To ascertain the viral dynamics in bats that lead to rapid transmission and infectivity in humans Objectives To understand the characteristics that bats possess, to host virulent pathogens To outline the mechanisms in bats in causing rapid transmission to humans

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.

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