Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.268
Filtrar
1.
J Colloid Interface Sci ; 630(Pt B): 1-10, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36308803

RESUMO

The ongoing COVID-19 (i.e., coronavirus) pandemic continues to adversely affect the human life, economy, and the world's ecosystem. Although significant progress has been made in developing antiviral materials for the coronavirus, much more work is still needed. In this work, N-functionalized graphene quantum dots (GQDs) were designed and synthesized as the antiviral nanomaterial for Feline Coronavirus NTU156 (FCoV NTU156) and Enterovirus 71 (EV71)) with ultra-high inhibition (>99.9%). To prepare the GQD samples, a unique solid-phase microwave-assisted technique was developed and the cell toxicity was established on the H171 and H184 cell lines after 72 h incubation, indicating superior biocompatibility. The surface functionality of GQDs (i.e., the phenolic and amino groups) plays a vital role in interacting with the receptor-binding-domain of the spike protein. It was also found that the addition of polyethylene glycol is advantageous for the dispersion and the adsorption of functionalized GQDs onto the virus surface, leading to an enhanced virus inhibition. The functionality of as-prepared GQD nanomaterials was further confirmed where a functionalized GQD-coated glass was shown to be extremely effective in hindering the virus spread for a relatively long period (>20 h).


Assuntos
COVID-19 , Enterovirus , Grafite , Pontos Quânticos , Humanos , Ecossistema , Antivirais/farmacologia
3.
BMC Infect Dis ; 22(1): 821, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348312

RESUMO

BACKGROUND: Poliomyelitis outbreaks due to pathogenic vaccine-derived polioviruses (VDPVs) are threatening and complicating the global polio eradication initiative. Most of these VDPVs are genetic recombinants with non-polio enteroviruses (NPEVs) of species C. Little is known about factors favoring this genetic macroevolution process. Since 2001, Madagascar has experienced several outbreaks of poliomyelitis due to VDPVs, and most of VDPVs were isolated in the south of the island. The current study explored some of the viral factors that can promote and explain the emergence of recombinant VDPVs in Madagascar. METHODS: Between May to August 2011, we collected stools from healthy children living in two southern and two northern regions of Madagascar. Virus isolation was done in RD, HEp-2c, and L20B cell lines, and enteroviruses were detected using a wide-spectrum 5'-untranslated region RT-PCR assay. NPEVs were then sequenced for the VP1 gene used for viral genotyping. RESULTS: Overall, we collected 1309 stools, of which 351 NPEVs (26.8%) were identified. Sequencing revealed 33 types of viruses belonging to three different species: Enterovirus A (8.5%), Enterovirus B (EV-B, 40.2%), and Enterovirus C (EV-C, 51.3%). EV-C species included coxsackievirus A13, A17, and A20 previously described as putative recombination partners for poliovirus vaccine strains. Interestingly, the isolation rate was higher among stools originating from the South (30.3% vs. 23.6%, p-value = 0.009). EV-C were predominant in southern sites (65.7%) while EV-B predominated in northern sites (54.9%). The factors that explain the relative abundance of EV-C in the South are still unknown. CONCLUSIONS: Whatever its causes, the relative abundance of EV-C in the South of Madagascar may have promoted the infections of children by EV-C, including the PV vaccine strains, and have favored the recombination events between PVs and NPEVs in co-infected children, thus leading to the recurrent emergence of recombinant VDPVs in this region of Madagascar.


Assuntos
Enterovirus Humano C , Infecções por Enterovirus , Enterovirus , Poliomielite , Vacinas contra Poliovirus , Poliovirus , Criança , Humanos , Madagáscar/epidemiologia , Filogenia , Infecções por Enterovirus/epidemiologia , Poliomielite/prevenção & controle , Enterovirus Humano C/genética , Surtos de Doenças , Vacina Antipólio Oral/efeitos adversos
4.
BMC Med ; 20(1): 436, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352415

RESUMO

BACKGROUND: A major hand-foot-and-mouth disease (HFMD) pathogen, coxsackievirus A16 (CVA16), has predominated in several of the last 10 years and caused the largest number of HFMD outbreaks between 2011 and 2018 in China. We evaluated the efficacy of maternal anti-CVA16 antibody transfer via the placenta and explored the dynamics of maternal and natural infection-induced neutralizing antibodies in children. METHODS: Two population-based longitudinal cohorts in southern China were studied during 2013-2018. Participants were enrolled in autumn 2013, including 2475 children aged 1-9 years old and 1066 mother-neonate pairs, and followed for 3 years. Blood/cord samples were collected for CVA16-neutralizing antibody detection. The maternal antibody transfer efficacy, age-specific seroprevalence, geometric mean titre (GMT) and immune response kinetics were estimated. RESULTS: The average maternal antibody transfer ratio was 0.88 (95% CI 0.80-0.96). Transferred maternal antibody levels declined rapidly (half-life: 2.0 months, 95% CI 1.9-2.2 months). The GMT decayed below the positive threshold (8) by 1.5 months of age. Due to natural infections, it increased above 8 after 1.4 years and reached 32 by 5 years of age, thereafter dropping slightly. Although the average duration of maternal antibody-mediated protection was < 3 months, the duration extended to 6 months on average for mothers with titres ≥ 64. CONCLUSIONS: Anti-CVA16 maternal antibodies are efficiently transferred to neonates, but their levels decline quickly. Children aged 0-5 years are the main susceptible population and should be protected by CVA16 vaccination, with the optimal vaccination time between 1.5 months and 1 year of age.


Assuntos
Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Criança , Recém-Nascido , Animais , Humanos , Lactente , Pré-Escolar , Estudos Soroepidemiológicos , Estudos Longitudinais , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Anticorpos Neutralizantes , China/epidemiologia , Estudos de Coortes
5.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361757

RESUMO

Enterovirus 71 (EV71) is the major etiological agent contributing to the development of hand-foot-mouth disease (HFMD). There are not any global available vaccines or antibody drugs against EV71 released yet. In this study, we perform the virus immunization in a cost-effective and convenient approach by preparing virus particles from size exclusion and immunization of chicken. Polyclonal yolk-immunoglobulin (IgY) was simply purified from egg yolk and monoclonal single-chain variable fragments (scFv) were selected via phage display technology with two scFv libraries containing 6.0 × 106 and 1.3 × 107 transformants. Specific clones were enriched after 5 rounds of bio-panning and four identical genes were classified after the sequence analysis. Moreover, the higher mutation rates were revealed in the CDR regions, especially in the CDR3. IgY showed specific binding activities to both EV71-infected and Coxsackievirus 16-infected cell lysates and high infectivity inhibitory activity of EV71. However, while IgY detected a 37 kDa protein, the selected scFv seemingly detected higher size proteins which could be cell protein instead of EV71 proteins. Despite the highly effective chicken antibody generation, the purity of virus particles prepared by size exclusion is the limitation of this study, and further characterization should be carried out rigorously.


Assuntos
Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Anticorpos de Cadeia Única , Animais , Vírion/genética , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/metabolismo , Gema de Ovo , Galinhas
6.
Commun Biol ; 5(1): 1293, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434067

RESUMO

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.


Assuntos
Enterovirus , Poliovirus , Vacinas de Partículas Semelhantes a Vírus , Poliovirus/metabolismo , Antivirais/farmacologia , Benzeno , Sítios de Ligação , Antígenos Virais , Glutationa/metabolismo , Sulfonamidas
7.
Nat Commun ; 13(1): 7280, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435844

RESUMO

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Recém-Nascido , Humanos , Pré-Escolar , Doença de Mão, Pé e Boca/epidemiologia , Estudos Prospectivos , Estudos Soroepidemiológicos , Infecções por Enterovirus/epidemiologia , China/epidemiologia , Antígenos Virais
8.
Int J Mol Sci ; 23(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36430203

RESUMO

Coxsackieviruses, a genus of enteroviruses in the small RNA virus family, cause fatal infectious diseases in humans. Thus far, there are no approved drugs to prevent these diseases. Human milk contains various biologically active components against pathogens. Currently, the potential activity of breast milk components against the coxsackievirus remains unclear. In our study, the inhibitory effect of 16 major human milk components was tested on coxsackievirus class A type 9 isolate (CV-A9), BUCT01; 2'-Fucosyllactose (2'-FL) was identified to be effective. Time-of-addition, attachment internalisation assays, and the addition of 2'-FL at different time points were applied to investigate its specific role in the viral life cycle. Molecular docking was used to predict 2'-FL's specific cellular targets. The initial screening revealed a significant inhibitory effect (99.97%) against CV-A9 with 10 mg/mL 2'-FL, with no cytotoxicity observed. Compared with the control group, 2'-FL blocked virus entry (85%) as well as inhibited viral attachment (48.4%) and internalisation (51.3%), minimising its infection in rhabdomyosarcoma (RD) cells. The cell pre-incubation with 2'-FL exhibited significant inhibition (73.2-99.9%). Extended incubation between cells with 2'-FL reduced CV-A9 infection (93.9%), suggesting that 2'-FL predominantly targets cells to block infection. Molecular docking results revealed that 2'-FL interacted with the attachment receptor αvß6 and the internalisation receptor FCGRT and ß2M with an affinity of -2.14, -1.87, and -5.43 kcal/mol, respectively. This study lays the foundation for using 2'-FL as a food additive against CV-A9 infections.


Assuntos
Infecções por Coxsackievirus , Enterovirus , Humanos , Ligação Viral , Simulação de Acoplamento Molecular
9.
Viruses ; 14(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36366459

RESUMO

Viral bivalve contamination is a recognized food safety hazard. Therefore, this study investigated the detection rates, seasonality, quantification, and genetic diversity of enteric viruses in bivalve samples (mussels and oysters). We collected 97 shellfish samples between March 2018 and February 2020. The screening of samples by qPCR or RT-qPCR revealed the detection of norovirus (42.3%), rotavirus A (RVA; 16.5%), human adenovirus (HAdV; 24.7%), and human bocavirus (HBoV; 13.4%). There was no detection of hepatitis A virus. In total, 58.8% of shellfish samples tested positive for one or more viruses, with 42.1% of positive samples contaminated with two or more viruses. Norovirus showed the highest median viral load (3.3 × 106 GC/g), followed by HAdV (median of 3.5 × 104 GC/g), RVA (median of 1.5 × 103 GC/g), and HBoV (median of 1.3 × 103 GC/g). Phylogenetic analysis revealed that norovirus strains belonged to genotype GII.12[P16], RVA to genotype I2, HAdV to types -C2, -C5, and -F40, and HBoV to genotypes -1 and -2. Our results demonstrate the viral contamination of bivalves, emphasizing the need for virological monitoring programs to ensure the quality and safety of shellfish for human consumption and as a valuable surveillance tool to monitor emerging viruses and novel variants.


Assuntos
Adenovírus Humanos , Bivalves , Infecções por Enterovirus , Enterovirus , Norovirus , Animais , Humanos , Brasil/epidemiologia , Filogenia , Norovirus/genética , Enterovirus/genética
10.
Viruses ; 14(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36366584

RESUMO

Many viruses are known to trigger endoplasmic reticulum (ER) stress in host cells, which in turn can develop a protective unfolded protein response (UPR). Depending on the conditions, the UPR may lead to either cell survival or programmed cell death. One of three UPR branches involves the upregulation of Xbp1 transcription factor caused by the unconventional cytoplasmic splicing of its mRNA. This process is accomplished by the phosphorylated form of the endoribonuclease/protein kinase Ire1/ERN1. Here, we show that the phosphorylation of Ire1 is up-regulated in HeLa cells early in enterovirus infection but down-regulated at later stages. We also find that Ire1 is cleaved in poliovirus- and coxsackievirus-infected HeLa cells 4-6 h after infection. We further show that the Ire1-mediated Xbp1 mRNA splicing is repressed in infected cells in a time-dependent manner. Thus, our results demonstrate the ability of enteroviruses to actively modulate the Ire1-Xbp1 host defensive pathway by inducing phosphorylation and proteolytic cleavage of the ER stress sensor Ire1, as well as down-regulating its splicing activity. Inactivation of Ire1 could be a novel mode of the UPR manipulation employed by viruses to modify the ER stress response in the infected cells.


Assuntos
Infecções por Enterovirus , Enterovirus , Humanos , Estresse do Retículo Endoplasmático , Endorribonucleases/genética , Endorribonucleases/metabolismo , Enterovirus/genética , Células HeLa , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/genética , Transdução de Sinais , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
11.
Medicine (Baltimore) ; 101(46): e31588, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401437

RESUMO

Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.


Assuntos
Enterovirus , Herpesvirus Humano 1 , Meningite Viral , Ácidos Nucleicos , Parechovirus , Vírus , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Estudos Transversais , Meningite Viral/diagnóstico , Meningite Viral/epidemiologia , Herpesvirus Humano 2 , Herpesvirus Humano 3
12.
Sci Rep ; 12(1): 17028, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36220850

RESUMO

After vaccination with enterovirus 71 (EV-A71), the prevalence of hand-foot-and-mouth disease (HFMD) remained high, and the spatial-temporal distribution of enteroviruses changed. Therefore, it is essential to define the temporal features, spatial distributions, and epidemiological and etiological characteristics of HFMD in Kunming. Between 2017 and 2020, a total of 36,540 children were diagnosed with HFMD in Kunming, including 32,754 children with enterovirus-positive clinical samples. Demographic, geographical, epidemiological and etiological data of the cases were acquired and analyzed. Other enteroviruses replaced EV-A71, and the incidence of EV-A71 decreased dramatically, whereas coxsackievirus A6 (CV-A6) and coxsackievirus A16 (CV-A16) had substantial outbreaks in 2018 and 2019, respectively. The major and minor peaks all extended for 2-4 months compared to before vaccination with the EV-A71 vaccine. From 2019 to 2020, CV-A6, as the predominant serotype, showed only a single peak. Although a high incidence of HFMD was observed in Guandu, Chenggong and Xishan, the annual incidence of different enterovirus serotypes was different in different regions. In 2017, other enteroviruses were most prevalent in Shilin. In 2018, CV-A16 and CV-A6 were most prevalent in Luquan and Shilin, respectively. In 2019, CV-A16 was most prevalent in Jinning. In 2020, CV-A6 and coxsackievirus A10 (CV-A10) were most prevalent in Luquan and Shilin, respectively. Meanwhile, the epidemic cycle of CV-A6 and CV-A16 was only 1 year, and CV-A10 and other enteroviruses were potential risk pathogens. The spatial and temporal distribution of HFMD varies at different scales, and the incidence of HFMD associated with different pathogens has obvious regional differences and seasonal trends. Therefore, research on multivalent combined vaccines is urgently needed, and proper preventive and protective measures could effectively control the incidence of HFMD-like diseases.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Febre Aftosa , Doença de Mão, Pé e Boca , Animais , Anticorpos Antivirais , Antígenos Virais , Benzenoacetamidas , Criança , China/epidemiologia , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Humanos , Lactente , Piperidonas , Sorogrupo , Vacinação , Vacinas Combinadas
13.
Front Public Health ; 10: 970880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238254

RESUMO

Objectives: This study aims to explore the interaction of different pathogens in Hand, foot and mouth disease (HFMD) by using a mathematical epidemiological model and the reported data in five regions of China. Methods: A cross-regional dataset of reported HFMD cases was built from four provinces (Fujian Province, Jiangsu province, Hunan Province, and Jilin Province) and one municipality (Chongqing Municipality) in China. The subtypes of the pathogens of HFMD, including Coxsackievirus A16 (CV-A16), enteroviruses A71 (EV-A71), and other enteroviruses (Others), were included in the data. A mathematical model was developed to fit the data. The effective reproduction number (R eff ) was calculated to quantify the transmissibility of the pathogens. Results: In total, 3,336,482 HFMD cases were collected in the five regions. In Fujian Province, the R eff between CV-A16 and EV-A71&CV-A16, and between CV-A16 and CV-A16&Others showed statistically significant differences (P < 0.05). In Jiangsu Province, there was a significant difference in R eff (P < 0.05) between the CV-A16 and Total. In Hunan Province, the R eff between CV-A16 and EV-A71&CV-A16, between CV-A16 and Total were significant (P < 0.05). In Chongqing Municipality, we found significant differences of the R eff (P < 0.05) between CV-A16 and CV-A16&Others, and between Others and CV-A16&Others. In Jilin Province, significant differences of the R eff (P < 0.05) were found between EV-A71 and Total, and between Others and Total. Conclusion: The major pathogens of HFMD have changed annually, and the incidence of HFMD caused by others and CV-A16 has surpassed that of EV-A71 in recent years. Cross-regional differences were observed in the interactions between the pathogens.


Assuntos
Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , China/epidemiologia , Infecções por Enterovirus/epidemiologia , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Incidência
14.
PLoS Pathog ; 18(10): e1010906, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36306280

RESUMO

As ultimate parasites, viruses depend on host factors for every step of their life cycle. On the other hand, cells evolved multiple mechanisms of detecting and interfering with viral replication. Yet, our understanding of the complex ensembles of pro- and anti-viral factors is very limited in virtually every virus-cell system. Here we investigated the proteins recruited to the replication organelles of poliovirus, a representative of the genus Enterovirus of the Picornaviridae family. We took advantage of a strict dependence of enterovirus replication on a host protein GBF1, and established a stable cell line expressing a truncated GBF1 fused to APEX2 peroxidase that effectively supported viral replication upon inhibition of the endogenous GBF1. This construct biotinylated multiple host and viral proteins on the replication organelles. Among the viral proteins, the polyprotein cleavage intermediates were overrepresented, suggesting that the GBF1 environment is linked to viral polyprotein processing. The proteomics characterization of biotinylated host proteins identified multiple proteins previously associated with enterovirus replication, as well as more than 200 new factors recruited to the replication organelles. RNA metabolism proteins, many of which normally localize in the nucleus, constituted the largest group, underscoring the massive release of nuclear factors into the cytoplasm of infected cells and their involvement in viral replication. Functional analysis of several newly identified proteins revealed both pro- and anti-viral factors, including a novel component of infection-induced stress granules. Depletion of these proteins similarly affected the replication of diverse enteroviruses indicating broad conservation of the replication mechanisms. Thus, our data significantly expand the knowledge of the composition of enterovirus replication organelles, provide new insights into viral replication, and offer a novel resource for identifying targets for anti-viral interventions.


Assuntos
Infecções por Enterovirus , Enterovirus , Poliovirus , Humanos , Enterovirus/metabolismo , Biotinilação , Poliovirus/fisiologia , Replicação Viral , Proteínas Virais/metabolismo , Poliproteínas/metabolismo , Antivirais/farmacologia , Fatores de Troca do Nucleotídeo Guanina/metabolismo
15.
J Med Chem ; 65(21): 14792-14808, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36254462

RESUMO

Enterovirus D68 (EV-D68) is a nonpolio enterovirus that is mainly transmitted through respiratory routes and poses a potential threat for large-scale spread. EV-D68 infections mostly cause moderate to severe respiratory diseases in children and potentially induce neurological diseases. However, there are no specific antiviral drugs or vaccines against EV-D68. Herein, through virtual screening and rational design, a series of novel quinoline analogues as anti-EV-D68 agents targeting VP1 were identified. Particularly, 19 exhibited potent antiviral activity with an EC50 value ranging from 0.05 to 0.10 µM against various EV-D68 strains and showed inhibition of viral replication verified by Western blot, immunofluorescence, and plaque formation assay. Mechanistic studies indicated that the anti-EV-D68 agents work mainly by interacting with VP1. The acceptable bioavailability of 23.9% in rats and significant metabolic stability in human liver microsome (Clint = 10.8 mL/min/kg, t1/2 = 148 min) indicated that compound 19 with a novel scaffold was worth further investigation.


Assuntos
Enterovirus Humano D , Infecções por Enterovirus , Enterovirus , Quinolinas , Infecções Respiratórias , Criança , Humanos , Ratos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Infecções por Enterovirus/tratamento farmacológico , Quinolinas/farmacologia , Quinolinas/uso terapêutico
17.
Virol J ; 19(1): 160, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224635

RESUMO

BACKGROUND: Enterovirus A (EV-A), such as enterovirus A71 (EV-A71), generally causes hand, foot, and mouth disease (HFMD). However, limited studies focused on uncommon enterovirus serotypes such as coxsackievirus A12 (CV-A12). This study aimed to provide evidence to determine the molecular characteristics of a CV-A12 strain isolated in Zhejiang province, China. METHODS: In routine surveillance of HFMD, we identified a child case with CV-A12 infection in 2019 in Zhejiang province, China. Enterovirus was examined by using real-time reverse transcription-PCR (qRT-PCR). A partial VP1 sequence was amplified to determine the serotype, and then a full-length CV-A12 genome was sequenced. Nucleotide and amino acid similarity was calculated with those CV-A12 strains available in GenBank. Recombination was detected using RDP 4 and SimPlot. Furthermore, phylogenetic analysis was conducted by using BEAST 1.10, and protein modeling was performed with I-TASSER webserver. RESULTS: A full-length CV-A12 genome PJ201984 was isolated in a Chinese child with HFMD. The similarities with complete coding sequences of the CV-A12 strains in GenBank ranged between 79.3-100% (nucleotide) and 94.4-100% (amino acid), whereas it was 88.7-100.0% (nucleotide) and 97.2-100% (amino acid) when excluding the CV-A12 prototype strain Texas-12. In PJ201984, amino acid variations were more divergent in P2 and P3 regions than those in P1; the majority of those variations in VP1 (13/15) and VP4 (7/8) were similar to those documented in recently isolated CV-A12 strains in China. Furthermore, recombination was identified in P2 region, which involved a CV-A5 strain collected in China. Phylogenetic analysis revealed that PJ201984 clustered together with multiple CV-A12 strains isolated in China and the Netherlands during 2013-2018, as compared to another cluster consisting of CV-A12 strains in China and France during 2009-2015. Additionally, protein models of VP1 and VP4 in PJ201984 were well predicted to be similar to VP1 protein of EV-A71 and VP4 protein of coxsackievirus A21, respectively. CONCLUSIONS: The full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Aminoácidos/genética , Criança , China/epidemiologia , Genótipo , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Nucleotídeos , Filogenia
18.
Adv Virus Res ; 113: 89-110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36307169

RESUMO

Enteroviruses are among the most common viral infectious agents of humans and cause a broad spectrum of illness, which can range from mild and self-limiting to severe. Severe outcomes of enteroviral infections can include aseptic meningitis, bronchitis, acute liver failure, hand-foot-mouth disease (HFMD), hemorrhagic conjunctivitis, or acute flaccid myelitis and other paralytic syndromes. Enteroviruses initiate their replicative life cycles by attaching to a broad range of cell surface receptors, which play direct roles in the clinical outcomes of enteroviral infections. In this chapter, we review the transmission and viral life cycle of enteroviruses and discuss the diverse cell surface receptors that facilitate enterovirus attachment, entry, or genome release.


Assuntos
Infecções por Enterovirus , Enterovirus , Mielite , Humanos , Enterovirus/genética
19.
Viruses ; 14(10)2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36298861

RESUMO

Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000-2003, 2005, 2007-2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5'-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16.


Assuntos
Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Vacinas , Camundongos , Animais , Filogenia , Taiwan/epidemiologia , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/prevenção & controle , Genótipo , Regiões 5' não Traduzidas , Soros Imunes , Anticorpos Neutralizantes/genética , China/epidemiologia , Enterovirus Humano A/genética
20.
Viruses ; 14(10)2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36298746

RESUMO

Enteroviruses are members of the Picornaviridae family consisting of human enterovirus groups A, B, C, and D as well as nonhuman enteroviruses. Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis, known as hand, foot, and mouth disease (HFMD), in children worldwide, especially in the Asia-Pacific region. EV71 and coxsackievirus A16 are the two viruses responsible for HFMD which are members of group A enteroviruses. The identified EV71 receptors provide useful information for understanding viral replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the respective viral genome that determine virulence remain unclear. Although a vaccine is currently approved, there is no effective therapy for treating EV71-infected patients. Therefore, understanding the host-pathogen interaction could provide knowledge in viral pathogenesis and further benefits to anti-viral therapy development. The aim of this study was to investigate the latest findings about the interaction of viral ligands with the host receptors as well as the activation of immunerelated signaling pathways for innate immunity and the involvement of different cytokines and chemokines during host-pathogen interaction. The study also examined the roles of viral proteins, mainly 2A and 3C protease, interferons production and their inhibitory effects.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Enterovirus Humano A/genética , Enterovirus/genética , Proteínas Virais/genética , Sítios Internos de Entrada Ribossomal , Interferons/genética , Antivirais/farmacologia , Citocinas/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...