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1.
West Afr J Med ; 40(1): 121-124, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36718761

RESUMO

Mankind has developed strategies to mitigate calamitous pandemics, by using vaccines. Eradication of some diseases was successful through usage of vaccines. Lassa, Yellow, Crimean-Congo, Marburg and Ebola viruses need special attention. Lassa fever, that now has a candidate vaccine, was discovered in 1969 when two missionary nurses died in Nigeria, while Yellow fever has a vaccine from its 17D attenuated strain. Crimean-Congo haemorrhagic fever is a widespread tick-borne viral disease, and the nucleoprotein and glycoproteins are identified for inclusion in a vaccine. Marburg virus is highly pathogenic with mortality rate of 90%. Ebola virus outbreak in West Africa in 2013-2016 necessitated an early introduction of a vaccine. The classical vaccine platforms are commonly used for human vaccines, and next-generation platforms, are being developed. Development of a novel multivalent vaccine against viral haemorrhagic fevers will eliminate the difficulties of single vaccines and may lead to the eradication of these diseases.


L'Humanité a développé des strategies pour atténuer les pandémiescalamiteuses, en utilisant des vaccins. L'éradication de certaines maladies a été réussie grâce à l'utilisation de vaccins. Les virus de Lassa, de la fièvre jaune, de la fièvre de Crimée-Congo, de Marburg et d'Ebola méritent une attention particulière. La fièvre de Lassa, qui dispose aujourd'hui d'un candidat vaccin, a été découverte en 1969 lors du décès de deux infirmières missionnaires au Nigeria, tandis que la fièvre jaune dispose d'un vaccin à partir de sa souche atténuée 17D. La fièvre hémorragique de Crimée-Congo est une maladie virale répandue, transmise par les tiques, et la nucléoprotéine et les glycoprotéines sont identifiées pour être incluses dans un vaccin. Le virus de Marburg est hautement pathogène avec un taux de mortalité de 90 %. L'épidémie de virus Ebola en Afrique de l'Ouest en 2013- 2016 a nécessité l'introduction rapide d'un vaccin. Les plateformes vaccinales classiques sont couramment utilisées pour les vaccins humains, et des plateformes de nouvelle sont en cours de développement. Le développement d'un nouveau vaccin multivalent contre les fièvres hémorragiques virales éliminera les difficultés des vaccins uniques et pourrait conduire à l'éradication de ces maladies. Mots clés: Innovant ; Multi-pathogène ; Développement de vaccins; Fièvres hémorragiques virales.

2.
Vaccine ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36702693

RESUMO

The increased demand for yellow fever (YF) vaccines over the last decade, along with insufficient availability of specific pathogen-free embryonated eggs required for timely vaccine production, has led to global YF vaccine shortages. A new live-attenuated YF vaccine candidate (generically referred to as vYF) cloned from a YF-VAX® vaccine (YF-17D vaccine) substrain adapted for growth in Vero cells cultured in serum-free media is currently in development. Here, we assessed the safety and immunogenicity of vYF, and its protective activity upon virulent challenge with wild-type yellow fever virus (YFV) Asibi, compared to licensed YF-17D vaccines in the translational cynomolgus macaque model. vYF was well tolerated with no major safety concerns. Vaccine-related safety observations were limited to minimal/minor microscopic findings at the injection sites and in the draining lymph nodes, consistent with expected stimulation of the immune system. vYF induced early differential expression of genes involved in antiviral innate immunity previously described in humans vaccinated with YF-17D vaccines, as well as YFV-specific IgM and IgG antibodies, high and sustained YFV neutralizing antibody titers from Day 14 up to at least Day 258 post-immunization, IgM+ and IgG+ memory B cells from Day 14 up to at least Day 221 post-vaccination, and Th1 interferon (IFN)-γ and interleukin (IL)-2 secreting effector and memory T cells. Additionally, vYF provided effective resistance to virulent challenge with wild-type YFV Asibi including complete protection against YFV-induced mortality, pathology, dysregulation of blood and liver soluble biomarkers, and a significant reduction in viremia and viral load to the limit of detection. These NHP data suggest that vYF would provide protection against YFV infection in practice, at least similar to that achieved with currently marketed YF-17D vaccines.

3.
Viruses ; 15(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36680231

RESUMO

Since late 2016, a yellow fever virus (YFV) variant carrying a set of nine amino acid variations has circulated in South America. Three of them were mapped on the methyltransferase (MTase) domain of viral NS5 protein. To assess whether these changes affected viral infectivity, we synthesized YFV carrying the MTase of circulating lineage as well as its isoform with the residues of the previous strains (NS5 K101R, NS5 V138I, and NS5 G173S). We observed a slight difference in viral growth properties and plaque phenotype between the two synthetic YFVs. However, the MTase polymorphisms associated with the Brazilian strain of YFV (2016-2019) confer more susceptibility to the IFN-I. In addition, in vitro MTase assay revealed that the interaction between the YFV MTase and the methyl donor molecule (SAM) is altered in the Brazilian MTase variant. Altogether, the results reported here describe that the MTase carrying the molecular signature of the Brazilian YFV circulating since 2016 might display a slight decrease in its catalytic activity but virtually no effect on viral fitness in the parameters comprised in this study. The most marked influence of these residues stands in the immune escape against the antiviral response mediated by IFN-I.


Assuntos
Interferon Tipo I , Vírus da Febre Amarela , Vírus da Febre Amarela/fisiologia , Interferon Tipo I/genética , Aminoácidos , Evasão da Resposta Imune , Brasil , Metiltransferases/metabolismo , Proteínas não Estruturais Virais/genética
4.
J Infect Public Health ; 16(3): 332-340, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36680848

RESUMO

Viral outbreaks still become global health challenges, for instance, influenza A viruses, Japanese encephalitis, Ebola virus, Yellow fever, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since 7 May 2022, another outbreak of monkeypox also has been reported in European countries and the United States. Meanwhile, the monkeypox virus is previously endemic only in the western and central parts of Africa. Monkeypox is a zoonotic disease, although the primary animal reservoir remains unknown. This article concisely reviews the monkeypox virus, its transmission, pathogenesis, and clinical manifestation, its changing global epidemiology before and during the current outbreak, and possible driving factors of the recent outbreak. Furthermore, we also discuss whether the monkeypox virus would become endemic beyond Africa. Even though the available data suggests that human-to-human transmission is currently happening and unconnected clusters exist, many efforts have been made to tackle this outbreak, such as active case detection, contact tracing, isolation, and postexposure vaccination.

5.
Vaccine X ; 13: 100256, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36686400

RESUMO

Understanding the level of investment needed for the next decade is vital to achieve the goal of Immunization Agenda 2030 (IA2030). Through the immunization funder perspective, this study estimates both global and regional economic resources required to achieve IA2030 coverage among 194 WHO member countries from 2021 to 2030, against 14 pathogens: Hepatitis B (Hep B), Haemophilus influenzae type b (Hib), Human papillomavirus (HPV), Japanese encephalitis (JE), Measles, Meningitis A (Men A), Streptococcus pneumoniae, Rotavirus, Rubella, Yellow Fever (YF), Diphtheria, Tetanus, Pertussis, and Tuberculosis. The total cost of immunization program, routine vaccine, routine delivery, and non-routine costs (SIA and stockpile) were estimated using WHO coverage forecast for IA2030. Incremental costs of achieving IA2030 for all vaccines and cost per immunized child were also assessed. All costs were calculated for each income and regional level, as well as global level. Scenario analysis and sensitivity analysis were conducted to account for uncertainty in future vaccine pricing and delivery costs. The total cost of immunization programs is $269.8 billion (95% confidence interval: $247.1 - $311.8), of which $152.8 billion is considered as routine vaccine cost, $114.9 billion is routine delivery cost. Non- routine cost for LICs and LMICs totaled $2.1 billion. The incremental cost of achieving coverage goals after 2020 is $89.9 billion ($27.7-$110.1), with upper-middle income countries requiring the largest increase in investment (56.2% of incremental costs). The average immunization cost per child across all countries is $192.6. Scenario analysis using the minimum and maximum vaccines price for fully self-financing countries resulted in total costs ranging from $193.6 and $552.2 billion. The immunization program cost among 194 WHO member countries is expected to increase during this decade. The strategy for resource mobilization and increasing investment from country governments and donors are essential to achieving IA2030 coverage and ensuring sustainable immunization programs.

6.
Cell Biosci ; 13(1): 9, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639652

RESUMO

BACKGROUND: Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive. RESULTS: We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus. CONCLUSION: Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36626059

RESUMO

Mosquitoes are a threat worldwide since they are vectors of important pathogens and parasites such as malaria, dengue, yellow fever, and West Nile. The residual toxicity of several commercial mosquito larvicides was evaluated for the control of Culex pipiens pipiens under controlled laboratory and semi-field conditions during late spring and summer of 2013. The evaluation included six different active ingredient formulations, i.e., diflubenzuron Du-Dim), Bacillus thuringiensis var. israelensis (Bti) (Vectobac), spinosad (Mozkill), S-methoprene (Biopren), temephos (Abate), and polydimethylsiloxane (PDMS) (Aquatain), that are currently registered of and had been registered in the past for mosquito control. Under controlled laboratory conditions, the residual activity ranged from 1 week (S-methoprene) up to 2 months (spinosad, PDMS). Exposure of larvicides under semi-field conditions resulted in noticeable differences regarding their efficacy as compared to the laboratory bioassays. Exposure of S-methoprene, Bti, and spinosad, for up to 3 days, resulted in similar adult emergence to the controls. On the other hand, the residual efficacy of diflubenzuron, temephos, and PDMS ranged from 14 to 28 days, depending on the season of exposure. Longevity and fecundity of adults that had emerged from surviving larvae, in most of the cases tested, did not differ significantly from that of the controls. The results of the present study demonstrate the necessity of both field and laboratory studies to draw safe conclusions regarding the efficacy of larvicides against mosquitoes and the selection of the proper formulation for each application scenario. In addition, defining the seasonal variation in the residual toxicity of the tested formulations could be useful for improving mosquitos' management programs.

8.
Arch Virol ; 168(2): 47, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609616

RESUMO

Brazil has experienced an increase in outbreaks caused by flaviviruses. The high incidence of dengue fever, the morbidity of Zika in children, and the high mortality of yellow fever have affected millions in recent years. Deciphering host-virus interactions is important for treating viral infections, and the mitogen-activated protein kinases (MAPK) are an interesting target because of their role in flavivirus replication. In particular, mitogen-activated protein kinase kinase (MEK), which targets extracellular-signal-regulated kinase (ERK), is necessary for dengue and yellow fever infections. In this study, we evaluated the role of the MEK/ERK pathway and the effect of the MEK inhibitor trametinib on the Asian ZIKV strain PE243 and the prototype African ZIKV strain MR766, addressing genome replication, morphogenesis, and viral release. ZIKV infection stimulated ERK phosphorylation in Vero cells at 12 and 18 hours postinfection (hpi). Trametinib showed sustained antiviral activity, inhibiting both ZIKV strains for at least four days, and electron microscopy showed probable inhibition of ZIKV morphogenesis. ZIKV PE243 can complete one cycle in Vero cells in 14 hours; genome replication was detected around 8 hpi, intracellular viral particles at 12 hpi, and extracellular progeny at 14 hpi. Treatments at 6-hour intervals showed that trametinib inhibited late stages of viral replication, and the titration of intra- or extracellular virions showed that the treatment especially affected viral morphogenesis and release. Thus, ZIKV stimulated ERK phosphorylation during viral morphogenesis and release, which correlated with trametinib inhibiting both the signaling pathway and viral replication.


Assuntos
Flavivirus , Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Chlorocebus aethiops , Criança , Humanos , Zika virus/genética , Células Vero , Febre Amarela/genética , MAP Quinases Reguladas por Sinal Extracelular , Quinases de Proteína Quinase Ativadas por Mitógeno , Replicação Viral/fisiologia
9.
Trop Dis Travel Med Vaccines ; 9(1): 1, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36707912

RESUMO

BACKGROUND: Yellow fever is a viral hemorrhagic fever caused by yellow fever virus, a mosquito-borne flavivirus. Despite an effective vaccine, major outbreaks continue to occur around the world. Even though it is not a proven neurotropic virus, neurological symptoms in more severe clinical forms are frequent. The understanding of this apparent paradox is still rarely addressed in literature. METHODS: The brains of thirty-eight patients with yellow fever confirmed by RT-PCR, who underwent autopsy, were analyzed morphologically to identify and characterize neuropathological changes. The data were compared with brains collected from individuals without the disease, as a control group. Both cases and controls were subdivided according to the presence or absence of co-concurrent septic shock, to exclude changes of the sepsis associated encephalopathy. To verify possible morphological differences between the yellow fever cases groups, between the control groups, and between the cases and the controls, we applied the statistical tests Fisher's exact test and chi-square, with p values < 0.05 considered statistically significant. RESULTS: All cases and controls presented, at least focally, neuropathological changes, which included edema, meningeal and parenchymal inflammatory infiltrate and hemorrhages, and perivascular inflammatory infiltrate. We did not find an unequivocal aspect of encephalitis. The only parameter that, after statistical analysis, can be attributed to yellow fever was the perivascular inflammatory infiltrate. CONCLUSIONS: The neuropathological findings are sufficient to justify the multiple clinical neurologic disturbances detected in the YF cases. Since most of the parameters evaluated did not show statistically significant difference between cases and controls, an explanation for most of the neuropathological findings may be the vascular changes, consequent to shock induced endotheliopathy, associated with stimulation of the immune system inherent to systemic infectious processes. The statistical difference obtained in yellow fever cases regarding perivascular infiltrate can be can be explained by the immune activation inherent to the condition.

10.
Infect Dis Now ; : 104654, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36709865

RESUMO

INTRODUCTION: Unvaccinated individuals in endemic areas with proven enzootic transmission of Yellow fever virus are at risk of infection due to a dramatic shift in the epidemiology of the disease over recent years. For this reason, epidemiological surveillance and laboratory confirmation of cases have become mandatory. OBJECTIVE: To develop and test a control RNA for YFV detection through real-time RT-PCR. METHODS: A 437-bp insert containing the T7 promoter and the target sequences for two different in-house protocols was designed in the context of the pUC57 vector and obtained through gene synthesis. After T7-driven in vitro transcription, standard curves were developed for Log10 serial dilutions of the YFV control RNA with 8 replicates. RESULTS: A dynamic range of quantification of 10 orders of magnitude was observed with a limit of detection of 6.3 GCE/µL (95% CI, 2.6 to 139.4 GCE/µL). CONCLUSION: The plasmid construct is available for YFV molecular test validation on clinical, entomological, and epizootic samples.

11.
Work ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36710698

RESUMO

BACKGROUND: The Arab region has witnessed different biological hazards, including cholera, yellow fever, and the COVID-19 pandemic. In addition, changes in rainfall and increased vegetation cover led to locust outbreaks in Tunisia, Libya, Morocco, and Saudi Arabia. This problem still exists and affects more than 20 countries and concerns indicate food shortages and food insecurity for more than 20 million people. OBJECTIVE: This study aimed to detect mental health problems related to climate change in the Arab world. METHODS: A cross-sectional descriptive survey was applied to determine the prevalence of mental health problems related to climate change (MHPCC). A random sample consisted of 1080 participants (523 male and 557 female), residents in 18 Arab countries; their ages ranged from 25 to 60 years. The Mental Health Problems related to Climate Change Questionnaire (MHPCCQ) was completed online. RESULTS: The results indicated average levels of MHPCC prevalence. The results also revealed no significant statistical differences in the MHPCC due to gender, educational class, and marital status except in climate anxiety; there were statistical differences in favor of married subgroup individuals. At the same time, there are statistically significant differences in the MHPCC due to the residing country variable in favor of Syria, Yemen, Algeria, Libya, and Oman regarding fears, anxiety, alienation, and somatic symptoms. In addition, Tunisia, Bahrain, Sudan, and Iraq were higher in climate depression than the other countries. CONCLUSION: The findings shed light on the prevalence of MHPCC in the Arab world and oblige mental health system workers, including policymakers, mental health providers, and departments of psychology in Arab universities, to take urgent action to assess and develop the system for mental health to manage the risks of extreme climate change on the human mental health.

12.
Eur J Med Chem ; 248: 115117, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36657300

RESUMO

Yellow fever disease is one of public health concerns in the tropics. Despite its significant medicinal and economic impact among large groups of the population, there is a lack of effective treatment against yellow fever. In this regard, here we describe the synthesis of a series of new 6-aryl-3-R-amino-1,2,4-triazin-5(4H)-ones and evaluation of their in vitro inhibitory activity against yellow fever virus. Among all tested compounds 4 derivatives possessing strong inhibitory activity at µM concentrations were identified. All the active compounds revealed a good toxicity profile. These facts make the compounds interesting candidates for further evaluation of their efficacy in the treatment of yellow fever virus infection in vivo.


Assuntos
Triazinas , Vírus da Febre Amarela , Triazinas/farmacologia , Antivirais/farmacologia
13.
BMC Pulm Med ; 23(1): 38, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707820

RESUMO

BACKGROUND: Disseminated cryptococcal infection is especially prone to occur in immunosuppressed hosts. We herein report the case of an immunosuppressed girl with disseminated cryptococcal infection in whom pulmonary cryptococcosis (PC) presented as diffuse cavitary pulmonary nodules, a finding which has rarely been reported. CASE PRESENTATION: A 16-year-old immunocompromised girl presented with fever and a non-productive cough. A chest computed tomography (CT) scan revealed diffuse pulmonary nodules with cavities. Subsequent results were consistent with disseminated cryptococcosis with Cryptococcus identified in her blood, bone marrow and cerebrospinal fluid cultures. Thus, the patient was diagnosed with disseminated cryptococcal infection with PC, cryptococcus meningitis, cryptococcus osteomyelitis and cryptococcus sepsis. After antifungal treatment, the patient demonstrated both clinical and chest radiological improvement. CONCLUSION: The atypical clinical manifestations of a disseminated cryptococcal infection and the rare manner of chest CT findings of PC reported in our case are easy to misdiagnose. It is necessary to carry out a thorough search for a definitive diagnosis using various methods.


Assuntos
Criptococose , Cryptococcus neoformans , Nódulos Pulmonares Múltiplos , Humanos , Feminino , Adolescente , Criptococose/diagnóstico , Criptococose/diagnóstico por imagem , Antifúngicos/uso terapêutico , Medula Óssea , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Hospedeiro Imunocomprometido
14.
Artigo em Inglês | MEDLINE | ID: mdl-36690390

RESUMO

In mosquitoes, the intradermal search for vertebrate blood (probing time) corresponds to the time taken from initial insertion of the mouthparts in the skin until visualization of the initial engorgement of blood in the midgut. Probing time evaluation provides useful information on the ability of a mosquito to initiate successful blood feeding. In this protocol, we describe how to determine feeding parameters in Aedes aegypti, a widely distributed mosquito that transmits several deadly pathogens, including yellow fever, dengue, Zika, and Chikungunya viruses. We focus on the different steps of a blood feeding event, including penetration, probing, interprobing, and feeding time. Penetration time corresponds to the insertion of the stylets into the host skin and usually lasts <10 sec. Probing time or intradermal search for blood involves saliva secretion into the skin. Some researchers group penetration and probing time as the exploratory phase for blood. Feeding time is an active phase of blood ingestion and engorgement. Feeding parameters depend on mosquito behaviors and these measurements are visually taken by the investigator. We include a video that provides a close look at a mosquito feeding event in which penetration, probing, and feeding times can be observed. To record these experimental times, one must closely watch the mosquito feeding behavior including stylet penetration in the host skin, visualization of the first traces of blood in the midgut, engorgement of the midgut, and removal of stylets from the skin.

15.
bioRxiv ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36712033

RESUMO

Insecticides have made great strides in reducing the global burden of vector-borne disease. Nonetheless, serious public health concerns remain because insecticide-resistant vector populations continue to spread globally. To circumvent insecticide resistance, it is essential to understand all contributing mechanisms. Contact-based insecticides are absorbed through the insect cuticle, which is comprised mainly of chitin polysaccharides, cuticular proteins, hydrocarbons, and phenolic biopolymers sclerotin and melanin. Cuticle interface alterations can slow or prevent insecticide penetration in a phenomenon referred to as cuticular resistance. Cuticular resistance characterization of the yellow fever mosquito, Aedes aegypti , is lacking. In the current study, we utilized solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy, gas chromatography/mass spectrometry (GC-MS), and transmission electron microscopy (TEM) to gain insights into the cuticle composition of congenic cytochrome P450 monooxygenase insecticide resistant and susceptible Ae. aegypti . No differences in cuticular hydrocarbon content or phenolic biopolymer deposition were found. In contrast, we observed cuticle thickness of insecticide resistant Ae. aegypti increased over time and exhibited higher polysaccharide abundance. Moreover, we found these local cuticular changes correlated with global metabolic differences in the whole mosquito, suggesting the existence of novel cuticular resistance mechanisms in this major disease vector.

16.
Braz. j. biol ; 83: e247604, 2023. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339370

RESUMO

Abstract In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.


Resumo No presente relatório, estudamos os possíveis inibidores de Covid-19 de constituintes bioativos de Centaurea jacea usando uma abordagem tripla que consiste em técnicas de química quântica, docking molecular e dinâmica molecular. Centaurea jacea é uma erva perene frequentemente usada em remédios populares de doenças dermatológicas e febre. Além disso, as propriedades anticâncer, antioxidante, antibacteriana e antiviral de seus compostos bioativos também são relatadas. A Mpro (proteases principais) foi acoplada a diferentes compostos de Centaurea jacea por meio de docking molecular. Todos os compostos estudados, incluindo apigenina, axilarina, Centaureidina, Cirsiliol, Eupatorina e Isokaempferide, mostram afinidades de ligação adequadas ao sítio de ligação da protease principal SARS-CoV-2 com suas energias de ligação -6,7 kcal / mol, -7,4 kcal / mol, - 7,0 kcal / mol, -5,8 kcal / mol, -6,2 kcal / mol e -6,8 kcal / mol, respectivamente. Dentre todos os compostos estudados, a axilarina apresentou eficiência máxima de inibidor, seguida pela Centaureidina, Isokaempferida, Apigenina, Eupatorina e Cirsiliol. Nossos resultados sugeriram que a axilarina se liga aos resíduos catalíticos mais cruciais CYS145 e HIS41 do Mpro, além disso a axilarina mostra 5 interações de ligações de hidrogênio e 5 interações hidrofóbicas com vários resíduos de Mpro. Além disso, os cálculos de dinâmica molecular em uma escala de tempo de 60 ns (6 × 106 femtossegundos) também mostraram percepções significativas sobre os efeitos de ligação da axilarina com Mpro de SARS-CoV-2 por imitação de proteínas como o ambiente aquoso. A partir de cálculos de dinâmica molecular, os cálculos RMSD e RMSF indicam a estabilidade e dinâmica do melhor complexo ancorado em ambiente aquoso. As propriedades ADME e a análise de previsão de toxicidade da axilarina também a recomendaram como um candidato a medicamento seguro. Além disso, as investigações in vivo e in vitro são essenciais para garantir a atividade anti-SARS-CoV-2 de todos os compostos bioativos, particularmente a axilarina, para encorajar o uso preventivo de Centaurea jacea contra infecções por Covid-19.


Assuntos
Humanos , Preparações Farmacêuticas , Centaurea , COVID-19 , Inibidores de Proteases , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , SARS-CoV-2
18.
J Cell Biochem ; 124(1): 127-145, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36502494

RESUMO

Numerous pathogens affecting human is present in the flavivirus family namely west nile, dengue, yellow fever, and zika which involves in development of global burden and distressing the environment economically. Till date, no approved drugs are available for targeting these viruses. The threat which urged the identification of small molecules for the inhibition of these viruses is the spreading of serious viral diseases. The recent outbreak of zika and dengue infections postured a solemn risk to worldwide public well-being. RNA-dependent RNA polymerase (RdRp) is the supreme adaptable enzymes of all the RNA viruses which is responsible for the replication and transcription of genome among the structural and nonstructural proteins of flaviviruses. It is understood that the RdRp of the flaviviruses are similar stating that the japanese encephalitis and west nile shares 70% identity with zika whereas the dengue serotype 2 and 3 shares the identity of 76% and 81%, respectively. In this study, we investigated the binding site of four flaviviral RdRp and provided insights into various interaction of the molecules using the computational approach. Our study helps in recognizing the potent compounds that could inhibit the viral protein as a common inhibitor. Additionally, with the conformational stability analysis, we proposed the possible mechanism of inhibition of the identified common small molecule toward RdRp of flavivirus. Finally, this study could be an initiative for the identification of common inhibitors and can be explored further for understanding the mechanism of action through in vitro studies for the study on efficacy.


Assuntos
Dengue , Flavivirus , Infecção por Zika virus , Zika virus , Humanos , Flavivirus/genética , Flavivirus/metabolismo , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Reposicionamento de Medicamentos , Proteínas Virais/metabolismo
19.
Rev Med Inst Mex Seguro Soc ; 61(1): 42-46, 2023 Jan 02.
Artigo em Espanhol | MEDLINE | ID: mdl-36542471

RESUMO

Background: The classification of respiratory triage is important, since its objective is reducing the risk of contagion and identifying the patient with respiratory symptoms. Objective: To compare the respiratory triage classification at admission of patients with COVID-19 and with the National Early Warning Score (NEWS) 2 scale. Material and methods: Observational, comparative, cross-sectional, retrospective study. 398 records of patients admitted to Respiratory Triage of a second level hospital were included. The triage color at admission was compared with the color in the re-classification with NEWS 2 scale. For the statistical analysis, percentages and frequencies were used; for qualitative variables, it was used chi-squared with a p value < 0.05. Results: The average age was 57 years. The most frequent gender was male with 60.3%, and their main signs and symptoms were dyspnea 45.7%, coughing 41.3% and fever 32.7%; for women, the frequency was 39.7% and the main symptoms were dyspnea 32.2%, coughing 26.5% and headache 23.9%. The most frequent comorbidities in male and female were, respectively, cardiovascular disease in 20.3% and 19.7%, type 2 diabetes in 17.9% and 14.5%, and chronic kidney disease in 5.2% and 4.7%. The classified color in Respiratory Triage with the highest percentaje at admission was yellow with 64.%; however, with the NEWS 2 re-classification the color with the highest percentage was red, with 50.8%. Conclusion: The classification was performed inadequately, since only 21.8% were compatible with both classifications.


Introducción: la clasificación de triage respiratorio es importante, pues tiene el objetivo de reducir el riesgo de contagio e identificar al paciente con síntomas respiratorios. Objetivo: comparar la clasificación de triage respiratorio al ingreso de pacientes con COVID-19 y con la escala National Early Warning Score (NEWS) 2. Material y métodos: estudio observacional, comparativo, transversal, retrospectivo y unicéntrico. Se incluyeron 398 expedientes de pacientes que ingresaron al Área de Triage Respiratorio de un hospital de segundo nivel. Se comparó el color del triage al ingreso con el color en la reclasificación utilizando la escala NEWS 2. Para el análisis estadístico, se usaron porcentajes y frecuencias; para variables cualitativas se usó chi cuadrada con un valor de p < 0.05. Resultados: la edad promedio fue de 57 años. Predominaron los hombres, con 60.3% y sus principales signos y síntomas fueron disnea 45.7%, tos 41.3% y fiebre 32.7%; hubo 39.7% de mujeres y sus síntomas fueron disnea 32.2%, tos 26.5% y cefalea 23.9%. Las comorbilidades más frecuentes en hombres y mujeres fueron: enfermedad cardiovascular 20.3 y 19.7%; diabetes tipo 2, 17.9 y 14.5%; enfermedad renal crónica, 5.2 y 4.7%, respectivamente. El color clasificado en triage respiratorio con mayor porcentaje a su ingreso fue amarillo con 64.6%; sin embargo, con la reclasificación de NEWS 2 el color con mayor porcentaje fue el rojo, con 50.8%. Conclusión: la clasificación del color se realizó de forma inadecuada, pues solo el 21.8% fueron compatibles con ambas clasificaciones.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , COVID-19/diagnóstico , COVID-19/epidemiologia , Triagem , Estudos Retrospectivos , Pandemias , Estudos Transversais , Hospitais , Dispneia , Serviço Hospitalar de Emergência
20.
Vaccine ; 41(3): 836-843, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36564277

RESUMO

Yellow fever vaccine associated neurovirulence and viscerotropism have been reported by various countries. In this study, the neurovirulence, viscerotropism and immunogenicity of yellow fever vaccine seed lots (master and working) and final product manufactured at Serum Institute of India (SII) were evaluated in cynomolgus monkeys. WHO reference virus 168-73 and Stamaril™ as a control vaccine was used for comparison. Neurovirulence and viscerotropism scores of the seed lots and final product were lower than Stamaril™. The SII seed virus and vaccine complies to the WHO requirement for neurovirulence, viscerotropism and immunogenicity, when tested in comparison to WHO reference seed virus 168/73. All challenged animals showed 100 % seroconversion as early as day 14 and neutralizing antibody titers were sustainable at day 30 in all animals.


Assuntos
Vacina contra Febre Amarela , Febre Amarela , Animais , Vírus da Febre Amarela , Febre Amarela/prevenção & controle , Primatas , Antígenos Virais , Vacinas Atenuadas
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