Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
J Med Virol ; 94(1): 88-98, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544348

ABSTRACT

The outbreak of the current coronavirus disease (COVID-19) occurred in late 2019 and quickly spread all over the world. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to a genetically diverse group that mutates continuously leading to the emergence of multiple variants. Although a few antiviral agents and anti-inflammatory medicines are available, thousands of individuals have passed away due to emergence of new viral variants. Thus, proper surveillance of the SARS-CoV-2 genome is needed for the rapid identification of developing mutations over time, which are of the major concern if they occur specifically in the surface spike proteins of the virus (neutralizing analyte). This article reviews the potential mutations acquired by the SARS-CoV2 since the pandemic began and their significant impact on the neutralizing efficiency of vaccines and validity of the diagnostic assays.


Subject(s)
COVID-19/epidemiology , Genetic Drift , Genome, Viral/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Antibodies, Neutralizing/immunology , Gene Frequency/genetics , Genetic Variation/genetics , Humans , Immunogenicity, Vaccine/immunology , Spike Glycoprotein, Coronavirus/genetics
2.
J R Soc Interface ; 18(184): 20210648, 2021 11.
Article in English | MEDLINE | ID: covidwho-1532630

ABSTRACT

We present methods for building a Java Runtime-Alterable-Model Platform (RAMP) of complex dynamical systems. We illustrate our methods by building a multivariant SEIR (epidemic) RAMP. Underlying our RAMP is an individual-based model that includes adaptive contact rates, pathogen genetic drift, waning and cross-immunity. Besides allowing parameter values, process descriptions and scriptable runtime drivers to be easily modified during simulations, our RAMP can used within R-Studio and other computational platforms. Process descriptions that can be runtime altered within our SEIR RAMP include pathogen variant-dependent host shedding, environmental persistence, host transmission and within-host pathogen mutation and replication. They also include adaptive social distancing and adaptive application of vaccination rates and variant-valency of vaccines. We present simulation results using parameter values and process descriptions relevant to the current COVID-19 pandemic. Our results suggest that if waning immunity outpaces vaccination rates, then vaccination rollouts may fail to contain the most transmissible variants, particularly if vaccine valencies are not adapted to deal with escape mutations. Our SEIR RAMP is designed for easy use by others. More generally, our RAMP concept facilitates construction of highly flexible complex systems models of all types, which can then be easily shared as stand-alone application programs.


Subject(s)
COVID-19 , Genetic Drift , Humans , Pandemics , SARS-CoV-2 , Vaccination
4.
Sci Rep ; 11(1): 18847, 2021 09 22.
Article in English | MEDLINE | ID: covidwho-1434148

ABSTRACT

As the SARS-CoV-2 has spread and the pandemic has dragged on, the virus continued to evolve rapidly resulting in the emergence of new highly transmissible variants that can be of public health concern. The evolutionary mechanisms that drove this rapid diversity are not well understood but neutral evolution should open the first insight. The neutral theory of evolution states that most mutations in the nucleic acid sequences are random and they can be fixed or disappear by purifying selection. Herein, we performed a neutrality test to better understand the selective pressures exerted over SARS-CoV-2 spike protein from homologue proteins of Betacoronavirus, as well as to the spikes from human clinical isolates of the virus. Specifically, Tyr and Asn have higher occurrence rates on the Receptor Binding Domain (RBD) and in the overall sequence of spike proteins of Betacoronavirus, whereas His and Arg have lower occurrence rates. The in vivo evolutionary phenomenon of SARS-CoV-2 shows that Glu, Lys, Phe, and Val have the highest probability of occurrence in the emergent viral particles. Amino acids that have higher occurrence than the expected by the neutral control, are favorable and are fixed in the sequence while the ones that have lower occurrence than expected, influence the stability and/or functionality of the protein. Our results show that most unique mutations either for SARS-CoV-2 or its variants of health concern are under selective pressures, which could be related either to the evasion of the immune system, increasing the virus' fitness or altering protein - protein interactions with host proteins. We explored the consequences of those selected mutations in the structure and protein - protein interaction with the receptor. Altogether all these forces have shaped the spike protein and the continually evolving variants.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Amino Acids/chemistry , Amino Acids/genetics , Angiotensin-Converting Enzyme 2/chemistry , Betacoronavirus/genetics , Evolution, Molecular , Genetic Drift , Glycosylation , Humans , Models, Theoretical , Mutation , Protein Binding/genetics , Spike Glycoprotein, Coronavirus/chemistry
5.
Cell ; 184(20): 5189-5200.e7, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1401295

ABSTRACT

The independent emergence late in 2020 of the B.1.1.7, B.1.351, and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three "501Y lineages" coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites, mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.


Subject(s)
COVID-19/epidemiology , Evolution, Molecular , Mutation , Pandemics , SARS-CoV-2/genetics , Amino Acid Sequence/genetics , COVID-19/immunology , COVID-19/transmission , COVID-19/virology , Codon/genetics , Genes, Viral , Genetic Drift , Host Adaptation/genetics , Humans , Immune Evasion , Phylogeny , Public Health
6.
Science ; 371(6534): 1139-1142, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-1063045

ABSTRACT

Zoonotic pandemics, such as that caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can follow the spillover of animal viruses into highly susceptible human populations. The descendants of these viruses have adapted to the human host and evolved to evade immune pressure. Coronaviruses acquire substitutions more slowly than other RNA viruses. In the spike glycoprotein, we found that recurrent deletions overcome this slow substitution rate. Deletion variants arise in diverse genetic and geographic backgrounds, transmit efficiently, and are present in novel lineages, including those of current global concern. They frequently occupy recurrent deletion regions (RDRs), which map to defined antibody epitopes. Deletions in RDRs confer resistance to neutralizing antibodies. By altering stretches of amino acids, deletions appear to accelerate SARS-CoV-2 antigenic evolution and may, more generally, drive adaptive evolution.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, Viral/genetics , COVID-19/virology , Immune Evasion , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Amino Acid Sequence , Amino Acid Substitution , Antigens, Viral/chemistry , Evolution, Molecular , Genetic Drift , Humans , Protein Conformation , Sequence Deletion , Spike Glycoprotein, Coronavirus/chemistry
7.
Health Secur ; 19(2): 195-208, 2021.
Article in English | MEDLINE | ID: covidwho-926569

ABSTRACT

Coronaviruses OC43, 229E, NL63, and HKU1 are endemic human respiratory coronaviruses that typically cause mild to moderate upper respiratory infections, similar to the common cold. They also may cause simple and complicated lower respiratory infections, otitis media, asthma exacerbations, gastroenteritis, and a few systemic complications. These viruses are usually seasonal (with winter dominance) and affect nearly all age groups. The seasonal and annual variation in virus prevalence has implications for understanding the concept of acquired immunity and its persistence or diminution. Coronaviruses generally have outbreak potential in susceptible populations of any age, particularly in patients with comorbidities, who tend to have increased clinical disease. These 4 coronaviruses are often found in the context of what appears to be coinfection with other pathogens, but especially other viruses. If coronaviruses are not specifically tested for, the sole detection of a viral copathogen would suggest the pathogen is the causative agent, when a coronavirus may be culpable, or both. The detection of these viruses in circumstances where respiratory viruses are generally sought in clinical samples is, therefore, justified. These pathogens can be chronically shed from the respiratory tract, which is more likely to occur among immunocompromised and complicated patients. These viruses share the potential for genetic drift. The genome is among the largest of RNA viruses, and the capability of these viruses to further change is likely underestimated. Given the potential disease among humans, it is justified to search for effective antiviral chemotherapy for these viruses and to consider uses in niche situations should effective therapy be defined. Whereas SARS-CoV-2 may follow the epidemiological pattern of SARS-CoV and extinguish slowly over time, there is yet concern that SARS-CoV-2 may establish itself as an endemic human respiratory coronavirus similar to OC43, 2299E, NL63, and HKU1. Until sufficient data are acquired to better understand the potential of SARS-CoV-2, continued work on antiviral therapy and vaccination is imperative.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/virology , Endemic Diseases , Respiratory Tract Infections/virology , COVID-19/complications , COVID-19/epidemiology , Coronavirus Infections/epidemiology , Disease Outbreaks , Genetic Drift , Humans , Prevalence , Respiratory Tract Infections/epidemiology , SARS-CoV-2/genetics , Seasons
8.
Evolution ; 74(12): 2549-2559, 2020 12.
Article in English | MEDLINE | ID: covidwho-852312

ABSTRACT

Following widespread infections of the most recent coronavirus known to infect humans, SARS-CoV-2, attention has turned to potential therapeutic options. With no drug or vaccine yet approved, one focal point of research is to evaluate the potential value of repurposing existing antiviral treatments, with the logical strategy being to identify at least a short-term intervention to prevent within-patient progression, while long-term vaccine strategies unfold. Here, we offer an evolutionary/population-genetic perspective on one approach that may overwhelm the capacity for pathogen defense (i.e., adaptation) - induced mutational meltdown - providing an overview of key concepts, review of previous theoretical and experimental work of relevance, and guidance for future research. Applied with appropriate care, including target specificity, induced mutational meltdown may provide a general, rapidly implemented approach for the within-patient eradication of a wide range of pathogens or other undesirable microorganisms.


Subject(s)
COVID-19/drug therapy , COVID-19/virology , Models, Genetic , Mutation , SARS-CoV-2/genetics , Antiviral Agents/therapeutic use , Evolution, Molecular , Extinction, Biological , Genetic Drift , Genome, Viral , Humans , Mutagenesis , Pandemics , SARS-CoV-2/pathogenicity , Selection, Genetic
9.
Head Neck ; 42(7): 1535-1538, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-343537

ABSTRACT

The COVID-19 epidemic was not the first coronavirus epidemic of this century and represents one of the increasing number of zoonoses from wildlife to impact global health. SARS CoV-2, the virus causing the COVID-19 epidemic is distinct from, but closely resembles SARS CoV-1, which was responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002. SARS CoV-1 and 2 share almost 80% of genetic sequences and use the same host cell receptor to initiate viral infection. However, SARS predominantly affected individuals in close contact with infected animals and health care workers. In contrast, CoV-2 exhibits robust person to person spread, most likely by means of asymptomatic carriers, which has resulted in greater spread of disease, overall morbidity and mortality, despite its lesser virulence. We review recent coronavirus-related epidemics and distinguish clinical and molecular features of CoV-2, the causative agent for COVID-19, and review the current status of vaccine trials.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Antibodies, Viral/immunology , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , Epitopes , Genetic Drift , Humans , Pandemics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus , Viral Vaccines , Whole Genome Sequencing
SELECTION OF CITATIONS
SEARCH DETAIL