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1.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 40: e2020335, 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1288038

RESUMEN

ABSTRACT Objective: To identify scientific knowledge about the attention to health surveillance and development of Brazilian children under the age of three years involving the Congenital Zika virus (ZIKV) Syndrome. Data sources: This is an integrative literature review of primary studies with Brazilian children under three years of age from 2015 to 2019. The searches were carried out in the databases Latin American and Caribbean Literature in Health Sciences (LILACS), US National Library of Medicine (PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), SCOPUS and Web of Science. It was carried out by crossing the keywords in English (child, child development and Zika virus) and in Portuguese (criança, desenvolvimento infantil e Zika vírus), with the combination of the Boolean operator "AND". Data synthesis: The knowledge produced is related to the specific health and development problems of children affected by the Congenital ZIKV Syndrome, with clinical characteristics, care demands, multiprofessional performance, health monitoring and surveillance needs. Conclusions: This integrative review synthesized scientific knowledge by adding aspects that reinforce the relevance of appropriate approaches to assess and care for children, linked to the engagement of caregivers, the need to document, evaluate and track the situations of children in early childhood and long-term, management coordination of care and its challenges in the context of primary health care.


RESUMO Objetivo: Identificar os conhecimentos científicos sobre a atenção à vigilância à saúde e o desenvolvimento de crianças brasileiras menores de três anos envolvendo a síndrome congênita do Zika vírus. Fontes de dados: Trata-se de uma revisão integrativa da literatura, do período de 2015 a 2019, de estudos primários com crianças brasileiras menores de três anos de idade. As buscas foram realizadas nas bases de dados Literatura Latino-Americana e do Caribe em Ciências da Saúde, National Library of Medicine, Cumulative Index to Nursing and Allied Health Literature, Scopus e Web of Science. Foi realizado cruzamento das palavras-chave em inglês (child, child development e Zika virus) e em português (criança, desenvolvimento infantil e Zika vírus), com a combinação do operador booleano and. Síntese dos dados: Os conhecimentos produzidos estão relacionados aos problemas específicos de saúde e desenvolvimento das crianças afetadas pela síndrome congênita do Zika vírus, com características clínicas, demandas de cuidados, atuação multiprofissional, necessidades de monitoramento e vigilância à saúde. Conclusões: Esta revisão integrativa sintetizou conhecimentos científicos adicionando aspectos que reforçam a relevância de abordagens adequadas para avaliar as crianças e cuidar delas, articulado ao engajamento dos cuidadores, à necessidade de documentar, avaliar e rastrear as situações das crianças na primeira infância e em longo alcance, à gestão coordenada do cuidado e aos seus desafios no contexto da atenção primária à saúde.

2.
Recurso de Internet en Portugués | LIS - Localizador de Información en Salud | ID: lis-48419

RESUMEN

Um microorganismo implantado em mosquitos reduziu em 70% a ocorrência de casos de dengue, 66% de incidência de casos de chinkungunya e 40% de Zika em Niterói, no Rio de Janeiro.


Asunto(s)
Dengue/prevención & control , Virus Zika , Planes y Programas de Investigación en Salud , Aedes , Wolbachia
3.
Int J Biol Macromol ; 190: 713-721, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34474053

RESUMEN

Zika virus (ZIKV) induces neurological and autoimmune complications such as microcephaly and Guillain-Barre syndrome. Effective vaccines are necessary to prevent the ZIKV infection. E protein of ZIKV is responsible for virus attachment, entry, and fusion. The domain III of E protein (EDIII) contains the neutralizing epitopes and is ideal to act as an antigen for ZIKV vaccine. However, EDIII is poorly immunogenic. CRM197 is a carrier protein and can activate T helper cells for EDIII. Mannan is a ligand of TLR-4 or TLR-2. Eight-arm PEG can link multiple EDIII molecules in one entity. In the present study, EDIII was covalently conjugated with CRM197, 8-arm PEG and mannan to improve the immunogenicity of EDIII. The conjugate (CRM-EDIII-PM) elicited high EDIII-specific antibody titers in the BALB/c mice. Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-5 and IL-10) were secreted at a marked level. Thus, CRM-EDIII-PM could stimulate potent humoral and cellular immune response to EDIII. The serum exposure of CRM-EDIII-PM to the immune system was prolonged. Moreover, CRM-EDIII-PM did not lead to apparent toxicity to the organs. Therefore, CRM-EDIII-PM was expected as a promising vaccine candidate for its ability to induce strong immune responses.

4.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166264, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34481867

RESUMEN

The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates.

5.
Infect Genet Evol ; 95: 105066, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34487865

RESUMEN

Managing emerging infectious diseases is a current challenge in the fields of microbiology and epidemiology. Indeed, among other environmental and human-related factors, climate change and global warming favor the emergence of new pathogens. The recent Zika virus (ZIKV) epidemic, of which the large and rapid spread surprised the scientific community, is a reminder of the importance to study viruses currently responsible for sporadic infections. Increasing our knowledge of key factors involved in emerging infections is essential to implement specific monitoring that can be oriented according to the pathogen, targeted population, or at-risk environment. Recent technological developments, such as high-throughput sequencing, genome-wide association studies and CRISPR screenings have allowed the identification of human single nucleotide polymorphisms (SNPs) involved in infectious disease outcome. This review focuses on the human genetic host factors that have been identified and shown to be associated with the pathogenesis of ZIKV infection and candidate SNP targets.

6.
PLoS Negl Trop Dis ; 15(9): e0009752, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34492017

RESUMEN

BACKGROUND: Biological control programs involving Wolbachia-infected Aedes aegypti are currently deployed in different epidemiological settings. New Caledonia (NC) is an ideal location for the implementation and evaluation of such a strategy as the only proven vector for dengue virus (DENV) is Ae. aegypti and dengue outbreaks frequency and severity are increasing. We report the generation of a NC Wolbachia-infected Ae. aegypti strain and the results of experiments to assess the vector competence and fitness of this strain for future implementation as a disease control strategy in Noumea, NC. METHODS/PRINCIPAL FINDINGS: The NC Wolbachia strain (NC-wMel) was obtained by backcrossing Australian AUS-wMel females with New Caledonian Wild-Type (NC-WT) males. Blocking of DENV, chikungunya (CHIKV), and Zika (ZIKV) viruses were evaluated via mosquito oral feeding experiments and intrathoracic DENV challenge. Significant reduction in infection rates were observed for NC-wMel Ae. aegypti compared to WT Ae. aegypti. No transmission was observed for NC-wMel Ae. aegypti. Maternal transmission, cytoplasmic incompatibility, fertility, fecundity, wing length, and insecticide resistance were also assessed in laboratory experiments. Ae. aegypti NC-wMel showed complete cytoplasmic incompatibility and a strong maternal transmission. Ae. aegypti NC-wMel fitness seemed to be reduced compared to NC-WT Ae. aegypti and AUS-wMel Ae. aegypti regarding fertility and fecundity. However further experiments are required to assess it accurately. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that the NC-wMel Ae. aegypti strain is a strong inhibitor of DENV, CHIKV, and ZIKV infection and prevents transmission of infectious viral particles in mosquito saliva. Furthermore, our NC-wMel Ae. aegypti strain induces reproductive cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, supporting field-releases in Noumea, NC.

7.
Bioorg Med Chem ; 47: 116392, 2021 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-34509861

RESUMEN

In recent years, dengue virus (DENV) and Zika virus (ZIKV), both mosquito-borne members of the Flaviviridae family, have emerged as intercontinental health issues since their vectors have spread from their tropical origins to temperate climate zones due to climate change and increasing globalization. DENV and ZIKV are positive-sense, single-stranded RNA viruses, whose genomes consist of three structural (capsid, membrane precursor, envelope) and seven non-structural (NS) proteins, all of which are initially expressed as a single precursor polyprotein. For virus maturation, the polyprotein processing is accomplished by host proteases and the viral NS2B/NS3 protease complex, whose inhibitors have been shown to be effective antiviral agents with loss of viral pathogenicity. In this work, we elucidate new structure-activity relationships of benzo[d]thiazole-based allosteric NS2B/NS3 inhibitors. We developed a new series of Y-shaped inhibitors, which, with its larger hydrophobic contact surface, should bind to previously unaddressed regions of the allosteric NS2B/NS3 binding pocket. By scaffold-hopping, we varied the benzo[d]thiazole core and identified benzofuran as a new lead scaffold shifting the selectivity of initially ZIKV-targeting inhibitors to higher activities towards the DENV protease. In addition, we were able to increase the ligand efficiency from 0.27 to 0.41 by subsequent inhibitor truncation and identified N-(5,6-dihydroxybenzo[d]thiazol-2-yl)-4-iodobenzamide as a novel sub-micromolar NS2B/NS3 inhibitor. Utilizing cell-based assays, we could prove the antiviral activity in cellulo. Overall, we report new series of sub-micromolar allosteric DENV and ZIKV inhibitors with good efficacy profile in terms of cytotoxicity and protease inhibition selectivity.

8.
J Med Microbiol ; 70(9)2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34499027

RESUMEN

Introduction. Zika virus (ZIKV) emerged as a public health concern on the American continent during late 2015. As the number of infected grew so did the concerns about its capability to cause long-term damage especially with the appearance of the congenital Zika syndrome (CZS). Proteins from the TAM family of receptor tyrosine kinases (RTKs) were proposed as the cellular receptors, however, due to the ability of the virus to infect a variety of cell lines different strategies to elucidate the tropism of the virus should be investigated.Hypothesis. Pseudotyping is a powerful tool to interrogate the ability of the glycoprotein (GP) to permit entry of viruses.Aim. We aimed to establish a highly tractable pseudotype model using lenti- and retro-viral backbones to investigate the entry pathway of ZIKV.Methodology. We used different glycoprotein constructs and different lenti- or retro-viral backbones, in a matrix of ratios to investigate production of proteins and functional pseudotypes.Results. Varying the ratio of backbone and glycoprotein plasmids did not yield infectious pseudotypes. Moreover, the supplementation of the ZIKV protease or the substitution of the backbone had no positive impact on the infectivity. We showed production of the proteins in producer cells implying the lack of infectious pseudotypes is due to a lack of successful glycoprotein incorporation, rather than lack of protein production.Conclusion. In line with other reports, we were unable to successfully produce infectious pseudotypes using the variety of methods described. Other strategies may be more suitable in the development of an efficient pseudotype model for ZIKV and other flaviviruses.


Asunto(s)
Glicoproteínas/genética , Proteínas Virales/genética , Virología/métodos , Infección por el Virus Zika/virología , Virus Zika/aislamiento & purificación , Glicoproteínas/metabolismo , Humanos , Proteínas Virales/metabolismo , Internalización del Virus , Virus Zika/clasificación , Virus Zika/genética , Virus Zika/fisiología
9.
Arch Dis Child ; 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34479857

RESUMEN

OBJECTIVE: Zika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls. DESIGN: Cohort study. SETTING: Public health centres in Grenada, West Indies. PATIENTS: 384 mother-child pairs were enrolled during a period of active ZIKV transmission (April 2016-March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child's exposure status. RESULTS: A total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays. CONCLUSIONS: Overall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.

10.
Cell Host Microbe ; 29(9): 1333-1335, 2021 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-34499857

RESUMEN

SARS-CoV-2 has mutually illuminated our collective knowledge and knowledge gaps, particularly in antiviral defense and therapeutic strategies. A recent study in Science (Poirier et al., 2021) uncovers an ancient antiviral mechanism that mammals utilize to suppress viruses, including SARS-CoV-2 and Zika virus, that could have broad implications for therapeutic strategies.

11.
Nat Commun ; 12(1): 5374, 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34508072

RESUMEN

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.

12.
Nat Commun ; 12(1): 5379, 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34508077

RESUMEN

Probabilistic forecasts play an indispensable role in answering questions about the spread of newly emerged pathogens. However, uncertainties about the epidemiology of emerging pathogens can make it difficult to choose among alternative model structures and assumptions. To assess the potential for uncertainties about emerging pathogens to affect forecasts of their spread, we evaluated the performance 16 forecasting models in the context of the 2015-2016 Zika epidemic in Colombia. Each model featured a different combination of assumptions about human mobility, spatiotemporal variation in transmission potential, and the number of virus introductions. We found that which model assumptions had the most ensemble weight changed through time. We additionally identified a trade-off whereby some individual models outperformed ensemble models early in the epidemic, but on average the ensembles outperformed all individual models. Our results suggest that multiple models spanning uncertainty across alternative assumptions are necessary to obtain robust forecasts for emerging infectious diseases.

13.
J Clin Neurophysiol ; 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34510092

RESUMEN

INTRODUCTION: Congenital Zika virus syndrome is a distinct pattern of birth defects in fetuses infected by the Zika virus. It presents a broad clinical spectrum that includes occurrences of microcephaly, hypertonia, dysphagia, hyperexcitability, seizures, and arthrogryposis. Imaging findings show neuronal migration disorders. METHODOLOGY: Case reports have suggested that arthrogryposis has a neurogenic cause. We analyzed needle electromyography and nerve conduction examinations on 77 patients aged 2-24 months presenting highly probable congenital Zika virus syndrome, with or without arthrogryposis. RESULTS: All those with arthrogryposis presented with chronic muscle denervation in the electromyography examination. Similarly, children with single or reversible joint abnormalities at birth showed the same findings. Denervation in the paravertebral musculature was found in all of the children with diaphragmatic paralysis or thoracic deformities. CONCLUSIONS: We propose that congenital contractures associated with congenital Zika virus syndrome are caused by the malformation of upper and lower motor neurons during embryogenesis.

14.
Sci Rep ; 11(1): 18000, 2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34504185

RESUMEN

Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive enzyme-linked immunosorbent assay (ELISA), using high-affinity unnatural-base-containing DNA (UB-DNA) aptamers that recognize the four categorized serotypes. Using UB-DNA aptamers specific to each serotype of dengue NS1 proteins (DEN-NS1), we developed our aptamer-antibody sandwich ELISA for dengue diagnostics. Furthermore, IgGs highly specific to DEN-NS1 inhibited the serotype-specific NS1 detection, inspiring us to develop the competitive ELISA format for dengue serotype-specific IgG detection. Blood samples from Singaporean patients with primary or secondary dengue infections confirmed the highly specific IgG detection of this format, and the IgG production initially reflected the serotype of the past infection, rather than the recent infection. Using this dengue competitive ELISA format, cross-reactivity tests of 21 plasma samples from Singaporean Zika virus-infected patients revealed two distinct patterns: 8 lacked cross-reactivity, and 13 were positive with unique dengue serotype specificities, indicating previous dengue infection. This antigen-detection ELISA and antibody-detection competitive ELISA combination using the UB-DNA aptamers identifies both past and current viral infections and will facilitate specific medical care and vaccine development for infectious diseases.

15.
Eur J Obstet Gynecol Reprod Biol ; 265: 162-168, 2021 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-34508989

RESUMEN

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted primarily by Aedes mosquitoes. ZIKV can be transmitted to humans by non-vector borne mechanisms such as sexual intercourse, maternal-foetal transmission or blood transfusion. In 2015, ZIKV emerged in the Americas, and spread to 87 countries and territories with autochthonous transmission, distributed across four of the six WHO regions. Most ZIKV infections in pregnancy are asymptomatic, but mother to child transmission of the virus can occur in 20 to 30% of cases and cause severe foetal and child defects. Children exposed to ZIKV while in utero might develop a pattern of structural anomalies and functional disabilities secondary to central nervous system damage, known as congenital Zika syndrome, and whose most common clinical feature is microcephaly. Normocephalic children born to mothers with ZIKV infection in pregnancy, and with no observable Zika-associated birth defects, may also present with later neurodevelopmental delay or post-natal microcephaly. Screening and detection of ZIKV infection in pregnancy is essential, because most women with ZIKV infection are asymptomatic and clinical manifestations are non-specific. However, the diagnosis of ZIKV infection poses multiple challenges due to limited resources and scarce laboratory capabilities in most affected areas, the narrow window of time that the virus persists in the bloodstream, the large proportion of asymptomatic infections, and the cross-reactivity with other flaviviruses such as Dengue virus (DENV). Molecular methods (RT-PCR) are the most reliable tool to confirm ZIKV infection, as serodiagnosis requires confirmation with neutralization tests in case of inconclusive or positive serology results. Prenatal ultrasound assessment is essential for monitoring foetal development and early detection of possible severe anomalies. A mid- and long-term follow-up of children exposed to ZIKV while in utero is necessary to promptly detect clinical manifestations of possible neurological impairment. Tweetable abstract: Zika virus infection during pregnancy is a cause of pregnancy loss and disability in children. Protection against mosquito bites, access to sexual and reproductive health services, prompt screening and detection of ZIKV infection in pregnancy, and prenatal ultrasound monitoring are key control strategies whilst a vaccine is not available.

16.
Policy Sci ; : 1-19, 2021 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-34511645

RESUMEN

Environmental threats increasingly entail important risks from government responses. In considering the risks of a new vector-borne disease, for example, decision-makers must also grapple with potential risks from responses such as the aerial spraying of pesticides. In communicating about these complex risks, public officials often choose different "frames" that promote different conceptualizations of the issue. Yet prior research has paid limited attention to how public officials frame the related risks of the environmental threat and the public response. This paper starts to fill that gap by conducting a content analysis of statements by public officials regarding risks from the threat of a local outbreak of the Zika virus in South Florida in 2016, as well as risks from the response of aerial pesticide spraying. Based on limited prior research, we hypothesize that public officials are likely to have adopted a "risk maximization" frame that stressed the high risks from exposure to Zika, but a "risk trade-off" frame when discussing aerial spraying. In actuality, we find that officials strongly favored a "reassurance" frame that downplayed both types of risks. Based on this analysis, we suggest framing strategies for disease outbreaks and other threats with potentially risky government responses may vary significantly depending on local contexts and that the South Florida experience was a missed opportunity to test the strategy of trade-off framing.

17.
J Anal Test ; : 1-16, 2021 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-34513131

RESUMEN

The first corona-pandemic, coronavirus disease 2019 (COVID-19) caused a huge health crisis and incalculable damage worldwide. Knowledge of how to cure the disease is urgently needed. Emerging immune escaping mutants of the virus suggested that it may be potentially persistent in human society as a regular health threat as the flu virus. Therefore, it is imperative to identify appropriate biomarkers to indicate pathological and physiological states, and more importantly, clinic outcomes. Proteins are the performers of life functions, and their abundance and modification status can directly reflect the immune status. Protein glycosylation serves a great impact in modulating protein function. The use of both unmodified and glycosylated proteins as biomarkers has also been proved feasible in the studies of SARS, Zika virus, influenza, etc. In recent years, mass spectrometry-based glycoproteomics, as well as proteomics approaches, advanced significantly due to the evolution of mass spectrometry. We focus on the current development of the mass spectrometry-based strategy for COVID-19 biomarkers' investigation. Potential application of glycoproteomics approaches and challenges in biomarkers identification are also discussed.

18.
J Biomol Struct Dyn ; : 1-18, 2021 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-34516356

RESUMEN

Congenital Zika virus syndrome has caused a public health emergency of international concern. So far, there are no drugs available to prevent or treat the infection caused by Zika virus. The Zika virus NS3 helicase is a potential protein target for drug discovery due to its vital role in viral genome replication. NS3 helicase unwinds the viral RNA to enable the reproduction of the viral genome by the NS5 protein. NS3 helicase has two crucial binding sites; the ATP binding site and the RNA binding site. We used molecular docking and molecular dynamics (MD) simulations to study the structural behavior of Zika virus NS3 helicase in its apo form and in the presence of ATP, single-stranded RNA, and both ATP-RNA to understand their potential implications in NS3 helicase activity. Further, we have carried out virtual screening of FDA approved drugs, followed by molecular docking to identify the ATP-competitive hit molecules as probable Zika virus NS3 helicase inhibitors. The MD simulations trajectories were analyzed using normal mode analysis and principal component analysis that reveals fluctuations in the R-loop. These findings aid in understanding the molecular mechanisms of the simultaneous binding of ATP and RNA, and guide the design and discovery of new inhibitors of the Zika virus NS3 helicase as a promising drug target to treat the Zika virus infection. Communicated by Ramaswamy H. Sarma.

19.
Front Immunol ; 12: 635701, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34489923

RESUMEN

Serological testing is a powerful tool in epidemiological studies for understanding viral circulation and assessing the effectiveness of virus control measures, as is the case of SARS-CoV-2, the pathogenic agent of COVID-19. Immunoassays can quantitatively reveal the concentration of antiviral antibodies. The assessment of antiviral antibody titers may provide information on virus exposure, and changes in IgG levels are also indicative of a reduction in viral circulation. In this work, we describe a serological study for the evaluation of antiviral IgG and IgM antibodies and their correlation with antiviral activity. The serological assay for IgG detection used two SARS-CoV-2 proteins as antigens, the nucleocapsid N protein and the 3CL protease. Cross-reactivity tests in animals have shown high selectivity for detection of antiviral antibodies, using both the N and 3CL antigens. Using samples of human serum from individuals previously diagnosed by PCR for COVID-19, we observed high sensitivity of the ELISA assay. Serological results with human samples also suggest that the combination of higher titers of antiviral IgG antibodies to different antigen targets may be associated with greater neutralization activity, which can be enhanced in the presence of antiviral IgM antibodies.


Asunto(s)
Anticuerpos Antivirales/inmunología , Prueba Serológica para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/prevención & control , Vigilancia Inmunológica , SARS-CoV-2/inmunología , Animales , Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , COVID-19/epidemiología , COVID-19/inmunología , Prueba Serológica para COVID-19/normas , Reacciones Cruzadas , Virus del Dengue/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/normas , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Ratones , Ratones Endogámicos BALB C , Sensibilidad y Especificidad , Virus Zika/inmunología
20.
Histochem Cell Biol ; 2021 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-34514517

RESUMEN

Structural changes of two patient-derived glioblastoma cell lines after Zika virus infection were investigated using scanning transmission electron tomography on high-pressure-frozen, freeze-substituted samples. In Zika-virus-infected cells, Golgi structures were barely visible under an electron microscope, and viral factories appeared. The cytosol outside of the viral factories resembled the cytosol of uninfected cells. The viral factories contained largely deranged endoplasmic reticulum (ER), filled with many so-called replication organelles consisting of a luminal vesicle surrounded by the ER membrane. Viral capsids were observed in the vicinity of the replication organelles (cell line #12537 GB) or in ER cisternae at large distance from the replication organelles (cell line #15747 GB). Near the replication organelles, we observed many about 100-nm-long filaments that may represent viral ribonucleoprotein complexes (RNPs), which consist of the RNA genome and N protein oligomers. In addition, we compared Zika-virus-infected cells with cells infected with a phlebovirus (sandfly fever Turkey virus). Zika virions are formed in the ER, whereas phlebovirus virions are assembled in the Golgi apparatus. Our findings will help to understand the replication cycle in the virus factories and the building of the replication organelles in glioblastoma cells.

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