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1.
Nature ; 602(7898): 671-675, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35016199

RESUMO

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/virologia , Evasão da Resposta Imune/imunologia , Imunização Secundária , SARS-CoV-2/imunologia , Adulto , Anticorpos Monoclonais/imunologia , Vacina BNT162/administração & dosagem , Vacina BNT162/imunologia , Bélgica , COVID-19/imunologia , COVID-19/transmissão , ChAdOx1 nCoV-19/administração & dosagem , ChAdOx1 nCoV-19/imunologia , Convalescença , Feminino , Humanos , Masculino , Mutação , Testes de Neutralização , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Viagem
2.
Proc Natl Acad Sci U S A ; 119(13): e2114619119, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35320047

RESUMO

SignificanceMicrobes colonizing the infant gut during the first year(s) of life play an important role in immune system development. We show that after birth the (nearly) sterile gut is rapidly colonized by bacteria and their viruses (phages), which often show a strong cooccurrence. Most viruses infecting the infant do not cause clinical signs and their numbers strongly increase after day-care entrance. The infant diet is clearly reflected by identification of plant-infecting viruses, whereas fungi and parasites are not part of a stable gut microbiota. These temporal high-resolution baseline data about the gut colonization process will be valuable for further investigations of pathogenic viruses, dynamics between phages and their bacterial host, as well as studies investigating infants with a disturbed microbiota.


Assuntos
Bacteriófagos , Microbioma Gastrointestinal , Microbiota , Vírus , Bactérias , Humanos , Lactente
3.
BMC Infect Dis ; 24(1): 1139, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390446

RESUMO

We investigate the emergence, mutation profile, and dissemination of SARS-CoV-2 lineage B.1.214.2, first identified in Belgium in January 2021. This variant, featuring a 3-amino acid insertion in the spike protein similar to the Omicron variant, was speculated to enhance transmissibility or immune evasion. Initially detected in international travelers, it substantially transmitted in Central Africa, Belgium, Switzerland, and France, peaking in April 2021. Our travel-aware phylogeographic analysis, incorporating travel history, estimated the origin to the Republic of the Congo, with primary European entry through France and Belgium, and multiple smaller introductions during the epidemic. We correlate its spread with human travel patterns and air passenger data. Further, upon reviewing national reports of SARS-CoV-2 outbreaks in Belgian nursing homes, we found this strain caused moderately severe outcomes (8.7% case fatality ratio). A distinct nasopharyngeal immune response was observed in elderly patients, characterized by 80% unique signatures, higher B- and T-cell activation, increased type I IFN signaling, and reduced NK, Th17, and complement system activation, compared to similar outbreaks. This unique immune response may explain the variant's epidemiological behavior and underscores the need for nasal vaccine strategies against emerging variants.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/virologia , COVID-19/epidemiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Idoso , Masculino , Viagem , Bélgica/epidemiologia , Pessoa de Meia-Idade , Feminino , Adulto , Filogeografia , Nasofaringe/virologia
4.
Virol J ; 20(1): 12, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658615

RESUMO

BACKGROUND: Only two cases of papillomavirus infections in North American porcupines (Erethizon dorsatum) have been described thus far, and molecular investigation linked these cases to two distinct papillomavirus species. METHODS: In this report, we present the clinical, histological and molecular investigation of a third case of a porcupine papillomavirus infection. Papillomatous lesions occurred on the upper and lower lip of an otherwise healthy three-year old female that was kept in captivity. Within one month, the lesions progressed into exophytic black nodules, followed by a temporary stabilization and ultimately spontaneous regression within seven months of their initial observation. PCR-based screening using specific primers for Erethizon dorsatum papillomavirus 1 and 2 revealed the presence of both these virus types, after which nanopore sequencing was used to determine the complete sequences of the two virus genomes. RESULTS: One of the genomes shares 99.9% similarity with the only known sequence for Erethizon dorsatum papillomavirus 1, while the second represents a distinct lineage of Erethizon dorsatum papillomavirus 2, sharing only 93.3% similarity with the previously discovered strain. CONCLUSIONS: This report marks the first observation of a papillomavirus co-infection in a North American porcupine, although the individual contribution of the two virus types to the clinical presentation was not assessed.


Assuntos
Coinfecção , Porcos-Espinhos , Animais , Feminino , Humanos , Pré-Escolar , Coinfecção/veterinária , Técnicas de Amplificação de Ácido Nucleico , América do Norte
5.
Virus Genes ; 59(6): 795-800, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37589804

RESUMO

Mpox is a viral zoonosis with endemic circulation in animals and humans in some West and Central African countries. The disease was imported a few times in the past to countries outside the African continent through infected animals or travelers, one of which resulted in an unprecedented global outbreak sustained by human-to-human transmission in 2022. Although timely and reliable diagnosis is a cornerstone of any disease control, availability of accurate diagnostic assays and comparative performance studies of diagnostic assays remains limited despite of the long-known identification of monkeypox virus (MPXV) as a human pathogen since 1970. We laboratory-developed a real-time PCR test (LDT) and evaluated its performance against the commercial TaqMan™ Monkeypox Virus Microbe Detection Assay (Applied Biosystems, Cat A50137). The limit of detection of the LDT was established at 1.2 genome copies/ml. The sensitivity and specificity of both assays were 99.14% and 100%, respectively, and both are capable of detecting both clade I and clade II of MPXV. Our results demonstrate the validity and accuracy of the LDT for confirmation of MPXV infection from lesion swabs samples.


Assuntos
Monkeypox virus , Mpox , Animais , Humanos , Monkeypox virus/genética , Mpox/diagnóstico , Surtos de Doenças , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade
6.
Mol Biol Evol ; 38(4): 1608-1613, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33316043

RESUMO

Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of SARS-CoV-2 have been generated and shared with the scientific community. The unparalleled volume of available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analyzed with gold-standard phylogeographic approaches. To tackle this practical limitation, we here describe and apply a rapid analytical pipeline to analyze the spatiotemporal dispersal history and dynamics of SARS-CoV-2 lineages. As a proof of concept, we focus on the Belgian epidemic, which has had one of the highest spatial densities of available SARS-CoV-2 genomes. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement.


Assuntos
COVID-19/transmissão , COVID-19/virologia , Genoma Viral , Filogeografia , SARS-CoV-2/genética , Bélgica , COVID-19/epidemiologia , Evolução Molecular , Genômica , Humanos , Funções Verossimilhança , Mutação , Isolamento de Pacientes , Filogenia , Distanciamento Físico , Análise Espaço-Temporal , Fluxo de Trabalho
7.
Virol J ; 19(1): 8, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991633

RESUMO

BACKGROUND: Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in clinical presentation on the one hand and the host dependent clinical outcome of BPV-1 infection on the other hand indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation. METHODS: In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees. RESULTS: We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of them cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis. CONCLUSIONS: By generating a significant amount of complete-length BPV genomes, we succeeded to introduce next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample.


Assuntos
Papillomavirus Bovino 1 , Doenças dos Cavalos , Sequenciamento por Nanoporos , Nanoporos , Infecções por Papillomavirus , Neoplasias Cutâneas , Animais , Teorema de Bayes , Papillomavirus Bovino 1/genética , DNA Viral/genética , Genômica , Cavalos , Filogenia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/veterinária
8.
Emerg Infect Dis ; 27(1): 76-84, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33350932

RESUMO

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We studied the relationship between KIR-human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4-003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.


Assuntos
Doença pelo Vírus Ebola , Alelos , Teorema de Bayes , Genótipo , Antígenos HLA , Doença pelo Vírus Ebola/epidemiologia , Humanos , Receptores KIR/genética
9.
BMC Genomics ; 19(1): 617, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115009

RESUMO

BACKGROUND: In the past decade, many new paramyxoviruses that do not belong to any of the seven established genera in the family Paramyxoviridae have been discovered. Amongst them are J-virus (JPV), Beilong virus (BeiPV) and Tailam virus (TlmPV), three paramyxovirus species found in rodents. Based on their similarities, it has been suggested that these viruses should compose a new genus, tentatively called 'Jeilongvirus'. RESULTS: Here we present the complete genomes of three newly discovered paramyxoviruses, one found in a bank vole (Myodes glareolus) from Slovenia and two in a single, co-infected Rungwe brush-furred rat (Lophuromys machangui) from Mozambique, that represent three new, separate species within the putative genus 'Jeilongvirus'. The genome organization of these viruses is similar to other paramyxoviruses, but like JPV, BeiPV and TlmPV, they possess an additional open reading frame, encoding a transmembrane protein, that is located between the F and G genes. As is the case for all Jeilongviruses, the G genes of the viruses described here are unusually large, and their encoded proteins are characterized by a remarkable amino acid composition pattern that is not seen in other paramyxoviruses, but resembles certain motifs found in Orthopneumovirus G proteins. CONCLUSIONS: The phylogenetic clustering of JPV, BeiPV and TlmPV with the viruses described here, as well as their shared features that set them apart from other paramyxoviruses, provide additional support for the recognition of the genus 'Jeilongvirus'.


Assuntos
Genoma Viral , Proteínas de Membrana/genética , Paramyxovirinae/classificação , Paramyxovirinae/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , Paramyxoviridae/classificação , Paramyxoviridae/genética , Filogenia , Análise de Sequência de DNA
10.
J Gen Virol ; 99(12): 1699-1704, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30355398

RESUMO

We report here the complete sequence and genome organization of a new papillomavirus, Erethizon dorsatum papillomavirus 2 (EdPV2), which was isolated from cutaneous lesions observed on the muzzle of a North American porcupine. The complete genome is 8809 nucleotides long and encodes five early (E6-E7-E1-E2-E4) and two late proteins (L2-L1). In addition to the upstream regulatory region, the EdPV2 genome contains an exceptionally large secondary non-coding region with no apparent functional relevance. EdPV2 is strongly divergent from the previously described porcupine papillomavirus EdPV1 and phylogenetic analysis shows EdPV2 clustering near members of the genus Pipapillomavirus, a group of rodent papillomaviruses. Pairwise sequence comparison based on the L1 open reading frame identifies Rattus norvegicus papillomavirus 1 as the closest related virus (59.97 % similarity). Based on its low sequence similarity to other known papillomaviruses, EdPV2 is thought to represent a new genus in the family Papillomaviridae.


Assuntos
Genoma Viral , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Filogenia , Roedores/virologia , Animais , Análise por Conglomerados , Ordem dos Genes , Tamanho do Genoma , Papillomaviridae/genética , Análise de Sequência de DNA , Homologia de Sequência , Proteínas Virais/genética , Sequenciamento Completo do Genoma
12.
Mol Ecol ; 25(23): 5994-6008, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27862516

RESUMO

Over the last decade, the recognized host range of hantaviruses has expanded considerably with the discovery of distinct hantaviruses in shrews, moles and bats. Unfortunately, in-depth studies of these viruses have been limited. Here we describe a comprehensive analysis of the spatial distribution, genetic diversity and evolution of Nova virus, a hantavirus that has the European mole as its natural host. Our analysis demonstrated that Nova virus has a high prevalence and widespread distribution in Belgium. While Nova virus displayed relatively high nucleotide diversity in Belgium, amino acid changes were limited. The nucleocapsid protein was subjected to strong purifying selection, reflecting the strict evolutionary constraints placed upon Nova virus by its host. Spatio-temporal analysis using Bayesian evolutionary inference techniques demonstrated that Nova virus had efficiently spread in the European mole population in Belgium, forming two distinct clades, representing east and west of Belgium. The influence of landscape barriers, in the form of the main waterways, on the dispersal velocity of Nova virus was assessed using an analytical framework for comparing Bayesian viral phylogenies with environmental landscape data. We demonstrated that waterways did not act as an environmental resistance factor slowing down Nova virus diffusion in the mole population. With this study, we provide information about the spatial diffusion of Nova virus and contribute sequence information that can be applied in further functional studies.


Assuntos
Infecções por Hantavirus/veterinária , Toupeiras/virologia , Orthohantavírus/genética , Filogenia , Animais , Teorema de Bayes , Bélgica , Infecções por Hantavirus/virologia , Análise Espaço-Temporal
13.
J Clin Virol ; 173: 105695, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38823290

RESUMO

Metagenomics is gradually being implemented for diagnosing infectious diseases. However, in-depth protocol comparisons for viral detection have been limited to individual sets of experimental workflows and laboratories. In this study, we present a benchmark of metagenomics protocols used in clinical diagnostic laboratories initiated by the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS). A mock viral reference panel was designed to mimic low biomass clinical specimens. The panel was used to assess the performance of twelve metagenomic wet lab protocols currently in use in the diagnostic laboratories of participating ENNGS member institutions. Both Illumina and Nanopore, shotgun and targeted capture probe protocols were included. Performance metrics sensitivity, specificity, and quantitative potential were assessed using a central bioinformatics pipeline. Overall, viral pathogens with loads down to 104 copies/ml (corresponding to CT values of 31 in our PCR assays) were detected by all the evaluated metagenomic wet lab protocols. In contrast, lower abundant mixed viruses of CT values of 35 and higher were detected only by a minority of the protocols. Considering the reference panel as the gold standard, optimal thresholds to define a positive result were determined per protocol, based on the horizontal genome coverage. Implementing these thresholds, sensitivity and specificity of the protocols ranged from 67 to 100 % and 87 to 100 %, respectively. A variety of metagenomic protocols are currently in use in clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implying the need for standardization of metagenomic analysis for use in clinical settings.


Assuntos
Benchmarking , Metagenômica , Sensibilidade e Especificidade , Vírus , Metagenômica/métodos , Metagenômica/normas , Humanos , Vírus/genética , Vírus/classificação , Vírus/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequenciamento de Nucleotídeos em Larga Escala/normas , Viroses/diagnóstico , Viroses/virologia , Biologia Computacional/métodos
14.
Virus Evol ; 9(2): vead065, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034864

RESUMO

In the future, zoonotic spillover events are expected to occur more frequently. Consequences of such events have clearly been demonstrated by recent outbreaks of monkeypox, Ebola virus, and the well-known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus discovery has proven to be an important tool in the preparation against viral outbreaks, generating data concerning the diversity, quantity, and ecology of the vertebrate virome. Orthoparamyxoviruses, a subfamily within the Paramyxoviridae, are important biosurveillance targets, since they include several known animal, human, and zoonotic pathogens such as Nipah virus, measles virus, and Hendra virus. During this study, 127 bat samples, thirty-four rodent samples, and seventeen shrew samples originating from Belgium were screened for orthoparamyxovirus presence using nested reverse transcription-polymerase chain reaction assays and nanopore sequencing. We present here the complete genomes of six putative new viral species, belonging to the genera Jeilongvirus and Henipavirus. Characterization of these genomes revealed significant differences in gene composition and organization, both within viruses of the same genus and between viruses of different genera. Remarkably, a previously undetected gene coding for a protein of unknown function was identified in the genome of a putative new Henipavirus. Additionally, phylogenetic analysis of jeilongviruses and henipaviruses reveals a division of both genera into two clades, one consisting of bat-borne viruses and the other consisting of rodent- and shrew-borne viruses, elucidating the need for proper reclassification.

15.
mBio ; 14(1): e0281522, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36625640

RESUMO

The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passaged in vitro in the presence of increasing concentrations of ALG-097161, a probe compound designed in the context of a 3CLpro drug discovery program. We identified a combination of amino acid substitutions in 3CLpro (L50F E166A L167F) that is associated with a >20× increase in 50% effective concentration (EC50) values for ALG-097161, nirmatrelvir (PF-07321332), PF-00835231, and ensitrelvir. While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6× to 72×). All substitutions are associated with a significant loss of enzymatic 3CLpro activity, suggesting a reduction in viral fitness. Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. These observations will be important for the interpretation of resistance development to 3CLpro inhibitors in the clinical setting. IMPORTANCE Paxlovid is the first oral antiviral approved for treatment of SARS-CoV-2 infection. Antiviral treatments are often associated with the development of drug-resistant viruses. In order to guide the use of novel antivirals, it is essential to understand the risk of resistance development and to characterize the associated changes in the viral genes and proteins. In this work, we describe for the first time a pathway that allows SARS-CoV-2 to develop resistance against Paxlovid in vitro. The characteristics of in vitro antiviral resistance development may be predictive for the clinical situation. Therefore, our work will be important for the management of COVID-19 with Paxlovid and next-generation SARS-CoV-2 3CLpro inhibitors.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Antivirais/farmacologia , Antivirais/química , Inibidores Enzimáticos , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , SARS-CoV-2/genética
16.
Nat Aging ; 3(6): 722-733, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37217661

RESUMO

Coronavirus Disease 2019 (COVID-19) vaccination has resulted in excellent protection against fatal disease, including in older adults. However, risk factors for post-vaccination fatal COVID-19 are largely unknown. We comprehensively studied three large nursing home outbreaks (20-35% fatal cases among residents) by combining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosol monitoring, whole-genome phylogenetic analysis and immunovirological profiling of nasal mucosa by digital nCounter transcriptomics. Phylogenetic investigations indicated that each outbreak stemmed from a single introduction event, although with different variants (Delta, Gamma and Mu). SARS-CoV-2 was detected in aerosol samples up to 52 d after the initial infection. Combining demographic, immune and viral parameters, the best predictive models for mortality comprised IFNB1 or age, viral ORF7a and ACE2 receptor transcripts. Comparison with published pre-vaccine fatal COVID-19 transcriptomic and genomic signatures uncovered a unique IRF3 low/IRF7 high immune signature in post-vaccine fatal COVID-19 outbreaks. A multi-layered strategy, including environmental sampling, immunomonitoring and early antiviral therapy, should be considered to prevent post-vaccination COVID-19 mortality in nursing homes.


Assuntos
COVID-19 , Humanos , Idoso , Filogenia , COVID-19/epidemiologia , SARS-CoV-2/genética , Casas de Saúde , Vacinação , Surtos de Doenças/prevenção & controle
17.
Antiviral Res ; 207: 105426, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36183903

RESUMO

Comparable to the related Ebola virus, Marburg virus is an emerging zoonotic pathogen that causes hemorrhagic fever with a high mortality rate. Therefore, handling of Ebola virus and Marburg virus is limited to biosafety level 4 facilities, of which only a limited number exists worldwide. However, researchers have developed several virus alternatives that are safe to handle in lower biosafety settings. One particularly interesting approach is the engineering of biologically contained Ebola virus by removing an essential gene from the virus genome and providing this missing gene in trans in a specific cell line. Because the virus is confined to this specific cell line, this results in a system that is safe to handle. So far, Ebola virus is the only virus for which biological containment has been reported. Here, we describe the first successful rescue of biologically contained Marburg virus and demonstrate that biological containment is also feasible for other filoviruses. Specifically, we describe the development of containment cell lines for Marburg virus through lentiviral transduction and show the growth and safety characteristics of eGFP-expressing, biologically contained Marburg virus in these cell lines. Additionally, we exploited this newly established Marburg virus system to screen over 500 compounds from available libraries. Lastly, we also validated the applicability of our biologically contained Marburg virus system in a 384-well format, to further illustrate the usefulness of this novel system as an alternative for high-throughput MARV screening of compound libraries.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Febres Hemorrágicas Virais , Doença do Vírus de Marburg , Marburgvirus , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Ebolavirus/genética , Doença pelo Vírus Ebola/tratamento farmacológico , Ensaios de Triagem em Larga Escala , Doença do Vírus de Marburg/tratamento farmacológico , Marburgvirus/fisiologia
18.
Antiviral Res ; 200: 105294, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35337896

RESUMO

Despite recent advancements in the development of vaccines and monoclonal antibody therapies for Ebola virus disease, treatment options remain limited. Moreover, management and containment of Ebola virus outbreaks is often hindered by the remote nature of the locations in which the outbreaks originate. Small-molecule compounds offer the advantage of being relatively cheap and easy to produce, transport and store, making them an interesting modality for the development of novel therapeutics against Ebola virus disease. Furthermore, the repurposing of small-molecule compounds, previously developed for alternative applications, can aid in reducing the time needed to bring potential therapeutics from bench to bedside. For this purpose, the Medicines for Malaria Venture provides collections of previously developed small-molecule compounds for screening against other infectious diseases. In this study, we used biologically contained Ebola virus to screen over 4,200 small-molecule drugs and drug-like compounds provided by the Medicines for Malaria Venture (i.e., the Pandemic Response Box and the COVID Box) and the Centre for Drug Design and Discovery (CD3, KU Leuven, Belgium). In addition to confirming known Ebola virus inhibitors, illustrating the validity of our screening assays, we identified eight novel selective Ebola virus inhibitors. Although the inhibitory potential of these compounds remains to be validated in vivo, they represent interesting compounds for the study of potential interventions against Ebola virus disease and might serve as a basis for the development of new therapeutics.


Assuntos
COVID-19 , Ebolavirus , Doença pelo Vírus Ebola , Antivirais/farmacologia , Antivirais/uso terapêutico , Vírus de DNA , Humanos
19.
J Virol Methods ; 304: 114512, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35257682

RESUMO

SARS-CoV-2 has kept the world in suspense for almost 2 years now. The virus spread rapidly worldwide and several variants of concern have emerged: Alpha, Beta, Gamma, Delta and recently Omicron. A rapid method to detect key mutations is needed because these variants may jeopardize the effectiveness of immune protection following vaccination or past infection. This article describes an easy, cheap and fast method for the detection of mutations in the spike protein that are indicative for specific variants. This method can easily distinguish Omicron from other variants.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Mutação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética
20.
Microbiol Resour Announc ; 11(2): e0116121, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35112910

RESUMO

We report the complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (lineage B.1.1.529) from a Belgian patient with a history of recent travel to Egypt. At the time of writing, this genome constituted the first confirmed case of an infection with the Omicron variant in Europe.

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