Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 314
Filter
Add filters

Document Type
Year range
1.
Signal Transduct Target Ther ; 6(1): 420, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585885

ABSTRACT

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Host-Pathogen Interactions/genetics , Receptors, Virus/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Gene Expression , HEK293 Cells , Host-Pathogen Interactions/immunology , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Protein Binding , Protein Domains , Receptors, Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Virus Replication
2.
Sci Rep ; 11(1): 24145, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1585802

ABSTRACT

Recent studies suggest that coronaviruses circulate widely in Southeast Asian bat species and that the progenitors of the SARS-Cov-2 virus could have originated in rhinolophid bats in the region. Our objective was to assess the diversity and circulation patterns of coronavirus in several bat species in Southeast Asia. We undertook monthly live-capture sessions and sampling in Cambodia over 17 months to cover all phases of the annual reproduction cycle of bats and test specifically the association between their age and CoV infection status. We additionally examined current information on the reproductive phenology of Rhinolophus and other bat species presently known to occur in mainland southeast China, Vietnam, Laos and Cambodia. Results from our longitudinal monitoring (573 bats belonging to 8 species) showed an overall proportion of positive PCR tests for CoV of 4.2% (24/573) in cave-dwelling bats from Kampot and 4.75% (22/463) in flying-foxes from Kandal. Phylogenetic analysis showed that the PCR amplicon sequences of CoVs (n = 46) obtained clustered in Alphacoronavirus and Betacoronavirus. Interestingly, Hipposideros larvatus sensu lato harbored viruses from both genera. Our results suggest an association between positive detections of coronaviruses and juvenile and immature bats in Cambodia (OR = 3.24 [1.46-7.76], p = 0.005). Since the limited data presently available from literature review indicates that reproduction is largely synchronized among rhinolophid and hipposiderid bats in our study region, particularly in its more seasonal portions (above 16° N), this may lead to seasonal patterns in CoV circulation. Overall, our study suggests that surveillance of CoV in insectivorous bat species in Southeast Asia, including SARS-CoV-related coronaviruses in rhinolophid bats, could be targeted from June to October for species exhibiting high proportions of juveniles and immatures during these months. It also highlights the need to develop long-term longitudinal surveys of bats and improve our understanding of their ecology in the region, for both biodiversity conservation and public health reasons.


Subject(s)
Alphacoronavirus/genetics , Betacoronavirus/genetics , COVID-19/transmission , Chiroptera/growth & development , SARS-CoV-2/genetics , Alphacoronavirus/classification , Animals , Asia, Southeastern/epidemiology , Betacoronavirus/classification , COVID-19/epidemiology , COVID-19/virology , Cambodia/epidemiology , Chiroptera/classification , Chiroptera/virology , Epidemics/prevention & control , Evolution, Molecular , Genome, Viral/genetics , Geography , Humans , Longitudinal Studies , Male , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/physiology , Species Specificity
3.
Viruses ; 13(12)2021 12 18.
Article in English | MEDLINE | ID: covidwho-1580423

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the causal agent of the COVID-19 pandemic that emerged in late 2019. The outbreak of variants with mutations in the region encoding the spike protein S1 sub-unit that can make them more resistant to neutralizing or monoclonal antibodies is the main point of the current monitoring. This study examines the feasibility of predicting the variant lineage and monitoring the appearance of reported mutations by sequencing only the region encoding the S1 domain by Pacific Bioscience Single Molecule Real-Time sequencing (PacBio SMRT). Using the PacBio SMRT system, we successfully sequenced 186 of the 200 samples previously sequenced with the Illumina COVIDSeq (whole genome) system. PacBio SMRT detected mutations in the S1 domain that were missed by the COVIDseq system in 27/186 samples (14.5%), due to amplification failure. These missing positions included mutations that are decisive for lineage assignation, such as G142D (n = 11), N501Y (n = 6), or E484K (n = 2). The lineage of 172/186 (92.5%) samples was accurately determined by analyzing the region encoding the S1 domain with a pipeline that uses key positions in S1. Thus, the PacBio SMRT protocol is appropriate for determining virus lineages and detecting key mutations.


Subject(s)
SARS-CoV-2/genetics , Sequence Analysis, DNA , Spike Glycoprotein, Coronavirus/genetics , COVID-19/virology , Genotype , Humans , Mutation , Protein Interaction Domains and Motifs/genetics , SARS-CoV-2/classification , Sequence Analysis, DNA/methods
4.
Rev Med Virol ; 31(6): e2231, 2021 11.
Article in English | MEDLINE | ID: covidwho-1574317

ABSTRACT

The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in Spike could affect efficacy of those treatments. Hence, monitoring of mutations is necessary to forecast and readapt the inventory of therapeutics. Different phylogenetic nomenclatures have been used for the currently circulating SARS-CoV-2 clades. The Spike protein has different hotspots of mutation and deletion, the most dangerous for immune escape being the ones within the receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, and N501Y. Convergent evolution has led to different combinations of mutations among different clades. In this review we focus on the main variants of concern, that is, the so-called UK (B.1.1.7), South African (B.1.351) and Brazilian (P.1) strains.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/therapy , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Antibodies, Viral/chemistry , Antibodies, Viral/metabolism , Antibodies, Viral/therapeutic use , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Gene Expression , Humans , Immune Evasion , Immunization, Passive/methods , Mutation , Phylogeny , Protein Binding , Risk Assessment , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , South Africa/epidemiology , Spike Glycoprotein, Coronavirus/immunology , United Kingdom/epidemiology
5.
Rev Med Virol ; 31(6): e2234, 2021 11.
Article in English | MEDLINE | ID: covidwho-1574124

ABSTRACT

The coronavirus disease (Covid-19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter-individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome-associated coronavirus, severe acute respiratory syndrome-associated coronavirus-2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti-inflammatory cytokines and might modulate the progression of Covid-19 in affected patients. Notably, genetic variations in innate immune components such as toll-like receptors and mannose-binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Genetic Predisposition to Disease , Influenza, Human/immunology , Respiratory Syncytial Virus Infections/immunology , Severe Acute Respiratory Syndrome/immunology , Antiviral Agents/therapeutic use , Biological Variation, Individual , COVID-19/drug therapy , COVID-19/genetics , COVID-19/virology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/genetics , Cytokine Release Syndrome/virology , Gene Expression , Humans , Immunity, Innate , Immunologic Factors/therapeutic use , Influenza, Human/drug therapy , Influenza, Human/genetics , Influenza, Human/virology , Mannose-Binding Lectin/genetics , Mannose-Binding Lectin/immunology , Orthomyxoviridae/drug effects , Orthomyxoviridae/immunology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/drug effects , Respiratory Syncytial Viruses/immunology , SARS Virus/drug effects , SARS Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology
6.
Nat Commun ; 12(1): 7239, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1574197

ABSTRACT

Controlling the SARS-CoV-2 pandemic becomes increasingly challenging as the virus adapts to human hosts through the continual emergence of more transmissible variants. Simply observing that a variant is increasing in frequency is relatively straightforward, but more sophisticated methodology is needed to determine whether a new variant is a global threat and the magnitude of its selective advantage. We present two models for quantifying the strength of selection for new and emerging variants of SARS-CoV-2 relative to the background of contemporaneous variants. These methods range from a detailed model of dynamics within one country to a broad analysis across all countries, and they include alternative explanations such as migration and drift. We find evidence for strong selection favoring the D614G spike mutation and B.1.1.7 (Alpha), weaker selection favoring B.1.351 (Beta), and no advantage of R.1 after it spreads beyond Japan. Cutting back data to earlier time horizons reveals that uncertainty is large very soon after emergence, but that estimates of selection stabilize after several weeks. Our results also show substantial heterogeneity among countries, demonstrating the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.


Subject(s)
COVID-19/virology , Mutation , SARS-CoV-2/classification , SARS-CoV-2/genetics , Humans , Japan , Models, Theoretical , Netherlands , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics , United Kingdom
7.
Viruses ; 13(12)2021 12 14.
Article in English | MEDLINE | ID: covidwho-1572669

ABSTRACT

Genotype screening was implemented in Italy and showed a significant prevalence of new SARS-CoV-2 mutants carrying Q675H mutation, near the furin cleavage site of spike protein. Currently, this mutation, which is expressed on different SARS-CoV-2 lineages circulating worldwide, has not been thoughtfully investigated. Therefore, we performed phylogenetic and biocomputational analysis to better understand SARS-CoV-2 Q675H mutants' evolutionary relationships with other circulating lineages and Q675H function in its molecular context. Our studies reveal that Q675H spike mutation is the result of parallel evolution because it arose independently in separate evolutionary clades. In silico data show that the Q675H mutation gives rise to a hydrogen-bonds network in the spike polar region. This results in an optimized directionality of arginine residues involved in interaction of spike with the furin binding pocket, thus improving proteolytic exposure of the viral protein. Furin was predicted to have a greater affinity for Q675H than Q675 substrate conformations. As a consequence, Q675H mutation could confer a fitness advantage to SARS-CoV-2 by promoting a more efficient viral entry. Interestingly, here we have shown that Q675H spike mutation is documented in all the VOCs. This finding highlights that VOCs are still evolving to enhance viral fitness and to adapt to the human host. At the same time, it may suggest Q675H spike mutation involvement in SARS-CoV-2 evolution.


Subject(s)
Furin/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Binding Sites , Genetic Fitness , Humans , Hydrogen Bonding , Molecular Dynamics Simulation , Mutation , Phylogeny , Protein Binding , Protein Conformation , SARS-CoV-2/classification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry
8.
PLoS One ; 16(12): e0261229, 2021.
Article in English | MEDLINE | ID: covidwho-1571989

ABSTRACT

In-depth study of the entire SARS-CoV-2 genome has uncovered many mutations, which have replaced the lineage that characterized the first wave of infections all around the world. In December 2020, the outbreak of variant of concern (VOC) 202012/01 (lineage B.1.1.7) in the United Kingdom defined a turning point during the pandemic, immediately posing a worldwide threat on the Covid-19 vaccination campaign. Here, we reported the evolution of B.1.1.7 lineage-related infections, analyzing samples collected from January 1st 2021, until April 15th 2021, in Friuli Venezia Giulia, a northeastern region of Italy. A cohort of 1508 nasopharyngeal swabs was analyzed by High Resolution Melting (HRM) and 479 randomly selected samples underwent Next Generation Sequencing analysis (NGS), uncovering a steady and continuous accumulation of B.1.1.7 lineage-related specimens, joined by sporadic cases of other known lineages (i.e. harboring the Spike glycoprotein p.E484K mutation). All the SARS-CoV-2 genome has been analyzed in order to highlight all the rare mutations that may eventually result in a new variant of interest. This work suggests that a thorough monitoring of the SARS-CoV-2 genome by NGS is essential to contain any new variant that could jeopardize all the efforts that have been made so far to resolve the emergence of the pandemic.


Subject(s)
COVID-19/diagnosis , Nasopharynx/virology , SARS-CoV-2/classification , Sequence Analysis, RNA/methods , COVID-19/epidemiology , Disease Outbreaks , High-Throughput Nucleotide Sequencing , Humans , Italy/epidemiology , Phylogeny , Phylogeography , RNA, Viral/genetics , SARS-CoV-2/genetics , United Kingdom/epidemiology
9.
Cell Rep ; 37(12): 110156, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1549680

ABSTRACT

The recently emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Beta (B.1.351) and Gamma (P.1) variants of concern (VoCs) include a key mutation (N501Y) found in the Alpha (B.1.1.7) variant that enhances affinity of the spike protein for its receptor, angiotensin-converting enzyme 2 (ACE2). Additional mutations are found in these variants at residues 417 and 484 that appear to promote antibody evasion. In contrast, the Epsilon variants (B.1.427/429) lack the N501Y mutation yet exhibit antibody evasion. We have engineered spike proteins to express these receptor binding domain (RBD) VoC mutations either in isolation or in different combinations and analyze the effects using biochemical assays and cryoelectron microscopy (cryo-EM) structural analyses. Overall, our findings suggest that the emergence of new SARS-CoV-2 variant spikes can be rationalized as the result of mutations that confer increased ACE2 affinity, increased antibody evasion, or both, providing a framework to dissect the molecular factors that drive VoC evolution.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , Cryoelectron Microscopy , Humans , Molecular Dynamics Simulation , Mutation , Protein Interaction Domains and Motifs , SARS-CoV-2/chemistry , SARS-CoV-2/classification , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
10.
Pediatr Infect Dis J ; 40(8): e310-e311, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1541587

ABSTRACT

The dynamics of intrafamilial spread of SARS-CoV-2 during January-February 2021 when variant B.1.1.7 predominated were compared with data from April to May 2020, when other circulating variants prevailed. Much higher intrafamilial transmission rates among all age groups, in particular in young children, and lower rates of sensory impairment were demonstrated during January-February 2021.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/classification , Adolescent , COVID-19/transmission , Child , Child, Preschool , Female , Humans , Hypesthesia/epidemiology , Hypesthesia/virology , Infant , Infant, Newborn , Israel/epidemiology , Male , SARS-CoV-2/genetics , Young Adult
12.
Microbiol Spectr ; 9(2): e0081621, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1526453

ABSTRACT

Reverse transcription-PCRs (RT-PCRs) targeting SARS-CoV-2 variant of concern (VOC) mutations have been developed to simplify their tracking. We evaluated an assay targeting E484K/N501Y to identify B.1.351/P1. Whole-genome sequencing (WGS) confirmed only 72 (59.02%) of 122 consecutive RT-PCR P.1/B.1.351 candidates. Prescreening RT-PCRs must target a wider set of mutations, updated from WGS data from emerging variants.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Diagnostic Errors/statistics & numerical data , Genome, Viral/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Humans , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/classification , Whole Genome Sequencing
13.
Microbiol Spectr ; 9(2): e0079221, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1526452

ABSTRACT

A wastewater surveillance program targeting a university residence hall was implemented during the spring semester 2021 as a proactive measure to avoid an outbreak of COVID-19 on campus. Over a period of 7 weeks from early February through late March 2021, wastewater originating from the residence hall was collected as grab samples 3 times per week. During this time, there was no detection of SARS-CoV-2 by reverse transcriptase quantitative PCR (RT-qPCR) in the residence hall wastewater stream. Aiming to obtain a sample more representative of the residence hall community, a decision was made to use passive samplers beginning in late March onwards. Adopting a Moore swab approach, SARS-CoV-2 was detected in wastewater samples just 2 days after passive samplers were deployed. These samples also tested positive for the B.1.1.7 (Alpha) variant of concern (VOC) using RT-qPCR. The positive result triggered a public health case-finding response, including a mobile testing unit deployed to the residence hall the following day, with testing of nearly 200 students and staff, which identified two laboratory-confirmed cases of Alpha variant COVID-19. These individuals were relocated to a separate quarantine facility, averting an outbreak on campus. Aggregating wastewater and clinical data, the campus wastewater surveillance program has yielded the first estimates of fecal shedding rates of the Alpha VOC of SARS-CoV-2 in individuals from a nonclinical setting. IMPORTANCE Among early adopters of wastewater monitoring for SARS-CoV-2 have been colleges and universities throughout North America, many of whom are using this approach to monitor congregate living facilities for early evidence of COVID-19 infection as an integral component of campus screening programs. Yet, while there have been numerous examples where wastewater monitoring on a university campus has detected evidence for infection among community members, there are few examples where this monitoring triggered a public health response that may have averted an actual outbreak. This report details a wastewater-testing program targeting a residence hall on a university campus during spring 2021, when there was mounting concern globally over the emergence of SARS-CoV-2 variants of concern, reported to be more transmissible than the wild-type Wuhan strain. In this communication, we present a clear example of how wastewater monitoring resulted in actionable responses by university administration and public health, which averted an outbreak of COVID-19 on a university campus.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , SARS-CoV-2/isolation & purification , Universities , Waste Water/virology , Wastewater-Based Epidemiological Monitoring , COVID-19/transmission , COVID-19/virology , Humans , Mass Screening , Ontario , Public Health , SARS-CoV-2/classification , SARS-CoV-2/genetics
14.
Nat Commun ; 12(1): 6405, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1505001

ABSTRACT

The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient's escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.


Subject(s)
COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Genome, Viral , Humans , Immune Evasion , Immunocompromised Host , Male , Middle Aged , Mutation , Neutralization Tests , Phylogeny , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
15.
Sci Rep ; 11(1): 21484, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500516

ABSTRACT

Epidemiological efforts to model the spread of SARS-CoV-2, the virus that causes COVID-19, are crucial to understanding and containing current and future outbreaks and to inform public health responses. Mutations that occur in viral genomes can alter virulence during outbreaks by increasing infection rates and helping the virus evade the host immune system. To understand the changes in viral genomic diversity and molecular epidemiology in Oxford during the first wave of infections in the United Kingdom, we analyzed 563 clinical SARS-CoV-2 samples via whole-genome sequencing using Nanopore MinION sequencing. Large-scale surveillance efforts during viral epidemics are likely to be confounded by the number of independent introductions of the viral strains into a region. To avoid such issues and better understand the selection-based changes occurring in the SARS-CoV-2 genome, we utilized local isolates collected during the UK's first national lockdown whereby personal interactions, international and national travel were considerably restricted and controlled. We were able to track the short-term evolution of the virus, detect the emergence of several mutations of concern or interest, and capture the viral diversity of the region. Overall, these results demonstrate genomic pathogen surveillance efforts have considerable utility in controlling the local spread of the virus.


Subject(s)
COVID-19/epidemiology , Genetic Variation , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19/virology , Genome, Viral , Humans , Phylogeny , Polymorphism, Single Nucleotide , Quarantine , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Seasons , Spike Glycoprotein, Coronavirus/genetics , United Kingdom/epidemiology , Whole Genome Sequencing
16.
Epidemiol Infect ; 149: e237, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1500393

ABSTRACT

The SARS-CoV-2 virus is rapidly evolving via mutagenesis, lengthening the pandemic, and threatening the public health. Until August 2021, 12 variants of SARS-CoV-2 named as variants of concern (VOC; Alpha to Delta) or variants of interest (VOI; Epsilon to Mu), with significant impact on transmissibility, morbidity, possible reinfection and mortality, have been identified. The VOC Delta (B.1.617.2) of Indian origin is now the dominant and the most contagious variant worldwide as it provokes a strong binding to the human ACE2 receptor, increases transmissibility and manifests considerable immune escape strategies after natural infection or vaccination. Although the development and administration of SARS-CoV-2 vaccines, based on different technologies (mRNA, adenovirus carrier, recombinant protein, etc.), are very promising for the control of the pandemic, their effectiveness and neutralizing activity against VOCs varies significantly. In this review, we describe the most significant circulating variants of SARS-CoV-2, and the known effectiveness of currently available vaccines against them.


Subject(s)
COVID-19 Vaccines/standards , COVID-19/prevention & control , SARS-CoV-2/genetics , Antibodies, Neutralizing , Antibodies, Viral/immunology , Humans , SARS-CoV-2/classification , SARS-CoV-2/immunology
17.
Trends Genet ; 37(12): 1069-1080, 2021 12.
Article in English | MEDLINE | ID: covidwho-1492657

ABSTRACT

Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is challenging. By examining the largest database of SARS-CoV-2 genomes The Global Initiative on Sharing Avian Influenza Data [GISAID; n >1.2 million high-quality (HQ) sequences], we present evidence suggesting that superspreading has had a key role in the epidemiological predominance of VOC. There are clear signatures in the database compatible with large superspreading events (SSEs) coinciding chronologically with the worst epidemiological scenarios triggered by VOC. The data suggest that, without the randomness effect of the genetic drift facilitated by superspreading, new VOC of SARS-CoV-2 would have had more limited chance of success.


Subject(s)
COVID-19 , Pandemics , SARS-CoV-2/classification , Animals , Humans
18.
J Virol ; 95(16): e0061721, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1486509

ABSTRACT

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.


Subject(s)
Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Mutation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Gene Expression , Host-Pathogen Interactions/genetics , Humans , Kinetics , Molecular Dynamics Simulation , Phenylalanine/chemistry , Phenylalanine/metabolism , Phylogeny , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , SARS-CoV-2/classification , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Thermodynamics , Valine/chemistry , Valine/metabolism , Virulence , Virus Attachment
19.
Virology ; 565: 29-37, 2022 01 02.
Article in English | MEDLINE | ID: covidwho-1475118

ABSTRACT

Bangladesh is the second-worst-affected country in South Asia by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study is to examine genome sequences from Bangladesh from January 2021 to June 2021 in order to monitor the SARS-CoV-2 VOC and the clades or lineages that are prevalent in the country. Within the study timeframe, at least eight Nextstrain clades were found: 20A, 20B, 20C, 20H (Beta, V2), 20I (Alpha, V1), 20 J (Gamma, V3), 21A (Delta), 21D (Eta), and six GISAID clades: four main (G, GH, GR, GRY) and two minors (GV, O) with an introduction of VOC B.1.1.7/Alpha, B.1.351/Beta and B.1.617.2/Delta. The introduction and recent occurrence of VOCs with substantial alterations in the receptor binding site of spike protein (K417 N, K417T, L452R, T478K, E484K, S494P, N501Y) are of particular importance. Specifically, VOC B.1.617.2/Delta has surpassed all prior VOCs in Bangladesh, posing a challenge to the existing disease management.


Subject(s)
COVID-19/virology , SARS-CoV-2/genetics , Bangladesh/epidemiology , Binding Sites , COVID-19/epidemiology , Female , Genome, Viral/genetics , Humans , Male , Mutation , Phylogeny , Prevalence , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/genetics
20.
Nat Commun ; 12(1): 6009, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1469968

ABSTRACT

By October 2021, 230 million SARS-CoV-2 diagnoses have been reported. Yet, a considerable proportion of cases remains undetected. Here, we propose GInPipe, a method that rapidly reconstructs SARS-CoV-2 incidence profiles solely from publicly available, time-stamped viral genomes. We validate GInPipe against simulated outbreaks and elaborate phylodynamic analyses. Using available sequence data, we reconstruct incidence histories for Denmark, Scotland, Switzerland, and Victoria (Australia) and demonstrate, how to use the method to investigate the effects of changing testing policies on case ascertainment. Specifically, we find that under-reporting was highest during summer 2020 in Europe, coinciding with more liberal testing policies at times of low testing capacities. Due to the increased use of real-time sequencing, it is envisaged that GInPipe can complement established surveillance tools to monitor the SARS-CoV-2 pandemic. In post-pandemic times, when diagnostic efforts are decreasing, GInPipe may facilitate the detection of hidden infection dynamics.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Genome, Viral , SARS-CoV-2/genetics , COVID-19/history , Europe/epidemiology , History, 21st Century , Humans , Incidence , Pandemics , Phylogeny , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Scotland , Switzerland , Victoria
SELECTION OF CITATIONS
SEARCH DETAIL
...