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1.
Cent Eur J Immunol ; 48(1): 35-42, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37206589

RESUMO

INTRODUCTION: During the last two and a half years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread around the world. Most of the SARS-CoV-2 vaccines are designed to produce anti-SARS-CoV-2 immunoglobulin G (IgG) against the viral S-glycoprotein. The aim of this study was to measure the anti-S antibody titres among the medical personnel who had been fully vaccinated with different types of vaccines, and to compare them with those who were COVID-19 convalescents. MATERIAL AND METHODS: In this study serum was collected from 261 healthcare workers, of whom 227 were vaccinated, while 34 were recovered participants who were not immunised. Serum samples were collected 21 days after the first dose and 60 and 180 days after the second dose of the vaccines and tested with a commercial ELISA kit. RESULTS: The highest antibody level (12 AU/ml) was measured in the Pfizer-BioNTech group, followed by Sinopharm (9.3 AU/ml), Sputnik V (5.9 AU/ml), Sinovac (4.6 AU/ml) and Oxford/Astra- Zeneca vaccine (2.5 AU/ml) 60 days after the second dose of the vaccines (90 days after the first dose). The seropositivity rate for mRNA vaccine was 88.5%, for vector vaccines 86.2% and for inactivated vaccines 71.4%. When comparing these antibody levels with COVID-19 convalescents, higher antibody titres were found in vaccinated participants (5.76 AU/ml vs 7.06 AU/ml), but the difference was not significant (p = 0.08). CONCLUSIONS: Individuals vaccinated with mRNA and vector vaccines had a higher seroconversion rate compared to the group vaccinated with inactivated vaccines, or convalescents.

2.
Molecules ; 28(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36903540

RESUMO

The interaction of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain with the host-cell ACE2 receptor is a well-known step in virus infection. Neuropilin-1 (NRP-1) is another host factor involved in virus internalization. The interaction between S-glycoprotein and NRP-1 has been identified as a potential COVID-19 treatment target. Herein, the effectiveness of folic acid and leucovorin in preventing contact between S-glycoprotein and NRP-1 receptors was investigated using in silico studies and then confirmed in vitro. The results of a molecular docking study showed that leucovorin and folic acid had lower binding energies than EG01377, a well-known NRP-1 inhibitor, and lopinavir. Two hydrogen bonds with Asp 320 and Asn 300 residues stabilized the leucovorin, while interactions with Gly 318, Thr 349, and Tyr 353 residues stabilized the folic acid. The molecular dynamic simulation revealed that the folic acid and leucovorin created very stable complexes with the NRP-1. The in vitro studies showed that the leucovorin was the most active inhibitor of the S1-glycoprotein/NRP-1 complex formation, with an IC75 value of 185.95 µg/mL. The results of this study suggest that folic acid and leucovorin could be considered as potential inhibitors of the S-glycoprotein/NRP-1 complex and, thus, could prevent the SARS-CoV-2 virus' entry into host cells.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Simulação de Acoplamento Molecular , Leucovorina , Neuropilina-1/metabolismo , Ácido Fólico/metabolismo , Internalização do Vírus , Tratamento Farmacológico da COVID-19 , Ligação Proteica , Glicoproteínas/metabolismo
3.
Molecules ; 27(16)2022 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-36014415

RESUMO

Since the outbreak of the COVID-19 pandemic, it has been obvious that virus infection poses a serious threat to human health on a global scale. Certain plants, particularly those rich in polyphenols, have been found to be effective antiviral agents. The effectiveness of Alchemilla viridiflora Rothm. (Rosaceae) methanol extract to prevent contact between virus spike (S)-glycoprotein and angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors was investigated. In vitro results revealed that the tested samples inhibited 50% of virus-receptor binding interactions in doses of 0.18 and 0.22 mg/mL for NRP1 and ACE2, respectively. Molecular docking studies revealed that the compounds from A. viridiflora ellagitannins class had a higher affinity for binding with S-glycoprotein whilst flavonoid compounds more significantly interacted with the NRP1 receptor. Quercetin 3-(6″-ferulylglucoside) and pentagalloylglucose were two compounds with the highest exhibited interfering potential for selected target receptors, with binding energies of -8.035 (S-glycoprotein) and -7.685 kcal/mol (NRP1), respectively. Furthermore, computational studies on other SARS-CoV-2 strains resulting from mutations in the original wild strain (V483A, N501Y-K417N-E484K, N501Y, N439K, L452R-T478K, K417N, G476S, F456L, E484K) revealed that virus internalization activity was maintained, but with different single compound contributions.


Assuntos
Alchemilla , Tratamento Farmacológico da COVID-19 , Alchemilla/química , Enzima de Conversão de Angiotensina 2 , Humanos , Simulação de Acoplamento Molecular , Mutação , Pandemias , Peptidil Dipeptidase A/metabolismo , Polifenóis/farmacologia , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus
4.
Viruses ; 14(7)2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35891358

RESUMO

Puumala orthohantavirus (PUUV) is endemic in Europe and can cause hemorrhagic fever with renal syndrome (nephropathia epidemica). Disease features include fever, thrombocytopenia, and acute kidney injury (AKI). This retrospective cohort study of forty PUUV patients aims to characterize associations of serum immunological, hemostatic or kidney injury markers to disease severity. While interleukin-18 (IL-18) was significantly increased in severely thrombocytopenic patients (<100 × 109 platelets/L) compared to patients with higher platelet counts, RANTES was significantly decreased in these patients. These data suggest that patients with significant thrombocytopenia might have experienced pronounced Th1 immune responses. When kidney dysfunction was used as the primary disease outcome, recently identified AKI biomarkers (Cystatin C, insulin-like growth factor-binding protein 7, Nephrin, and trefoil factor 3) were significantly upregulated in patients with severe PUUV infection, defined as the estimated glomerular filtration rate (eGFR) below 30 m/min/1.73 m2. The increased expression of these markers specifically indicates pathology in glomeruli and proximal tubuli. Furthermore, E-selectin was significantly higher while interferon gamma-induced protein 10 (IP-10) was significantly lower in PUUV patients with more severe kidney dysfunction compared to patients with higher eGFR-values. Increased E-selectin illustrates the central role of endothelial cell activation, whereas decreased IP-10 could indicate a less important role of this cytokine in the pathogenesis of kidney dysfunction.


Assuntos
Injúria Renal Aguda , Febre Hemorrágica com Síndrome Renal , Virus Puumala , Trombocitopenia , Injúria Renal Aguda/patologia , Biomarcadores , Quimiocina CXCL10 , Estudos de Coortes , Selectina E , Humanos , Rim/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombocitopenia/complicações
5.
J Glob Antimicrob Resist ; 29: 99-104, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35182775

RESUMO

OBJECTIVES: Brucellosis is a ubiquitous emergent bacterial zoonotic disease causing significant human morbidity in Bosnia and Herzegovina. So far, a high rate of resistant Brucella has been found worldwide. This study prospectively analysed the rates of resistance among human Brucella melitensis strains isolated in Bosnia and Herzegovina. METHODS: This study included 108 B. melitensis isolates from 209 patients diagnosed at five medical centres in Bosnia and Herzegovina. The resistance profiles of the B. melitensis isolates for the 13 most commonly used antimicrobials were studied in standard Brucella broth (BB) and cation-adjusted Mueller-Hinton broth (CAMHB) supplemented with 4% lysed horse blood or 5% defibrinated sheep blood. RESULTS: Of the 209 patients, B. melitensis blood cultures were positive for 111 (53.1%). Among the 108 isolates investigated, 91 (84.3%) were resistant to trimethoprim-sulfamethoxazole on BB, but not on either CAMHB. Nearly all isolates (>90%) were resistant to azithromycin on BB and both CAMHBs. CONCLUSION: We observed a high rate of B. melitensis resistance to azithromycin. The high rate of resistance to trimethoprim-sulfamethoxazole that we observed was related to BB, so an alternative broth should be used, such as the enriched CAMHBs in this study, for evaluating resistance to trimethoprim-sulfamethoxazole. Whole-genome sequencing studies are needed to understand the development of antimicrobial resistance in B. melitensis strains isolated from humans.


Assuntos
Anti-Infecciosos , Brucella melitensis , Animais , Antibacterianos/farmacologia , Azitromicina , Bósnia e Herzegóvina , Farmacorresistência Bacteriana , Cavalos , Humanos , Testes de Sensibilidade Microbiana , Ovinos , Combinação Trimetoprima e Sulfametoxazol
6.
Bioorg Chem ; 114: 105145, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246969

RESUMO

The novel coronavirus disease (Covid-19) has become a major health threat globally. The interaction of SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) with ACE2 receptor on host cells was recognized as the first step of virus infection and therefore as one of the primary targets for novel therapeutics. Pomegranate extracts are rich sources of bioactive polyphenols that were already recognized for their beneficial health effects. In this study, both in silico and in vitro methods were employed for evaluation of pomegranate peel extract (PoPEx), their major polyphenols, as well as their major metabolite urolithin A, to attenuate the contact of S-glycoprotein RBD and ACE2. Our results showed that PoPEx, punicalin, punicalagin and urolithin A exerted significant potential to block the S-glycoprotein-ACE2 contact. These in vitro results strongly confirm the in silico predictions and provide a valuable insight in the potential of pomegranate polyphenols for application in SARS-CoV-2 infection.


Assuntos
Misturas Complexas/farmacologia , Polifenóis/farmacologia , Punica granatum/química , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Cromatografia Líquida de Alta Pressão , Misturas Complexas/química , Frutas/química , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo
7.
Bosn J Basic Med Sci ; 21(4): 484-487, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577445

RESUMO

This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing severe acute respiratory syndrome coronavirus 2 epidemic. Whole genome sequence of four samples from coronavirus disease 2019 (COVID-19) outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, and England). The constructed phylogenetic tree indicates possible multiple independent introduction events. The data presented contribute to a better understanding of COVID-19 in the current reemergence of the disease.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , Humanos , Filogenia , SARS-CoV-2/classificação , Sequenciamento Completo do Genoma
8.
Bosn J Basic Med Sci ; 21(1): 111-116, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091331

RESUMO

Between March 5th and July 25th, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10,090, corresponding to a cumulative incidence rate of 285.7/100,000 population. Demographic and clinical information on all the cases along with exposure and contact information were collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number Rt, and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0%(790/5646) in the Federation of Bosnia and Herzegovina (FBH) and 6.2% (267/4299) in the Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the instantaneous reproduction number increased from 1.13 on May 20th to 1.72 on May 31st. The outbreak concerns both entities, FBH and RS, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.


Assuntos
COVID-19/epidemiologia , Surtos de Doenças , Saúde Pública/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Número Básico de Reprodução , Bósnia e Herzegóvina/epidemiologia , Criança , Pré-Escolar , Planejamento em Desastres , Feminino , Geografia , Hospitalização , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Quarentena , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
9.
Mol Cell Biochem ; 476(2): 1179-1193, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33200379

RESUMO

The search for effective coronavirus disease (COVID-19) therapy has attracted a great deal of scientific interest due to its unprecedented health care system overload worldwide. We have carried out a study to investigate the in silico effects of the most abundant pomegranate peel extract constituents on the multi-step process of serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) internalization in the host cells. Binding affinities and interactions of ellagic acid, gallic acid, punicalagin and punicalin were studied on four selected protein targets with a significant and confirmed role in the process of the entry of virus into a host cell. The protein targets used in this study were: SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2, furin and transmembrane serine protease 2. The results showed that the constituents of pomegranate peel extracts, namely punicalagin and punicalin had very promising potential for significant interactions with the selected protein targets and were therefore deemed good candidates for further in vitro and in vivo evaluation.


Assuntos
Tratamento Farmacológico da COVID-19 , Extratos Vegetais/química , Polifenóis/química , Punica granatum/química , COVID-19/virologia , Biologia Computacional , Humanos , Extratos Vegetais/uso terapêutico , Polifenóis/uso terapêutico , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos/efeitos dos fármacos , SARS-CoV-2/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/química , Internalização do Vírus/efeitos dos fármacos
10.
Indian J Med Microbiol ; 38(3 & 4): 415-420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33154256

RESUMO

Background: This study looked at the characteristics and outcomes of critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the Western Balkans in the post-pandemic period. Materials and Methods: This retrospective observational study of medical records and associated data collected during the post-pandemic period included all mechanically ventilated adult patients of two university-affiliated hospitals of the Western Balkans between 1 January and 31 March 2019 who had influenza A (H1N1) pdm09 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasopharyngeal swab specimens and respiratory secretions. Results: The study included 89 patients, 49 males (55.1%), aged 56.09 ± 12.64 years. The median time from shift from hospital time to intensive care unit was 1 day (range: 1-2). In the post-pandemic period, cases observed in this study were found to have the following comorbidities: cardiovascular diseases in 44 (49.4%) patients and diabetes in 21 (23.6%) patients. Thirty-one patients (34.8%) in this study were obese. All 89 patients (100%) experienced some degree of acute respiratory distress syndrome, and 39 (44%) had multiorgan failure. Eighty-three patients (93%) were intubated and mechanically ventilated, 6 (7%) received non-invasive mechanical ventilation, 12 (13%) were treated with vvECMO and 36 (40%) received renal replacement therapy. Vasoactive support was needed by 56 (63%) patients. The median duration of mechanical ventilation was 9 (6-15.5) days. The hospital mortality rate was 44%. Conclusion: Critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the post-pandemic season were older, required vasoactive drugs more often, and there was a trend of higher survival compared to H1N1 infection patients in the previous pandemic seasons.


Assuntos
Doenças Cardiovasculares/complicações , Complicações do Diabetes/epidemiologia , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Obesidade/complicações , Síndrome do Desconforto Respiratório/complicações , Adulto , Idoso , Península Balcânica/epidemiologia , Doenças Cardiovasculares/epidemiologia , Comorbidade , Oxigenação por Membrana Extracorpórea , Feminino , Humanos , Influenza Humana/terapia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Terapia de Substituição Renal , Respiração Artificial , Síndrome do Desconforto Respiratório/epidemiologia , Vasoconstritores/uso terapêutico
11.
Med Glas (Zenica) ; 17(2): 265-274, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602300

RESUMO

Aim The damage caused by the COVID-19 pandemic has made the prevention of its further spread at the top of the list of priorities of many governments and state institutions responsible for health and civil protection around the world. This prevention implies an effective system of epidemiological surveillance and the application of timely and effective control measures. This research focuses on the application of techniques for modelling and geovisualization of epidemic data with the aim of simple and fast communication of analytical results via geoportal. Methods The paper describes the approach applied through the project of establishing the epidemiological location-intelligence system for monitoring the effectiveness of control measures in preventing the spread of COVID-19 in Bosnia and Herzegovina. Results Epidemic data were processed and the results related to spatio-temporal analysis of the infection spread were presented by compartmental epidemic model, reproduction number R, epi-curve diagrams as well as choropleth maps for different levels of administrative units. Geovisualization of epidemic data enabled the release of numerous information from described models and indicators, providing easier visual communication of the spread of the disease and better recognition of its trend. Conclusion The approach involves the simultaneous application of epidemic models and epidemic data geovisualization, which allows a simple and rapid evaluation of the epidemic situation and the effects of control measures. This contributes to more informative decision-making related to control measures by suggesting their selective application at the local level.


Assuntos
Controle de Doenças Transmissíveis , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Análise Espaço-Temporal , Betacoronavirus , Bósnia e Herzegóvina/epidemiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Visualização de Dados , Epidemias , Monitoramento Epidemiológico , Mapeamento Geográfico , Sistemas de Informação em Saúde , Humanos , Modelos Estatísticos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , SARS-CoV-2
12.
Acta Microbiol Immunol Hung ; 67(3): 176-181, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32160781

RESUMO

Tigecycline can be effective to treat infections of carbapenem-resistant Acinetobacter baumannii (CRAB) however, no interpretive criteria have been approved so far. The objectives of this study were to evaluate the proportion of CRAB isolates and to compare gradient test with a broth microdilution (BMD) method for tigecycline susceptibility testing of A. baumannii.This study included 349 multidrug-resistant (MDR) Acinetobacter spp. collected from Serbia, Montenegro, Bosnia and Herzegovina in 2016 and 2017. Antibiotic susceptibility testing was performed by disk diffusion, VITEK2, gradient, ComASP Colistin. Tigecycline susceptibilities were interpreted according to breakpoints of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA).Majority of the tested isolates were CRAB (92.8%). Tigecycline MIC50/MIC90 values were 4/8 µg/mL by BMD and 0.5/4 µg/mL by gradient test. Essential agreement for BMD and gradient test amounted to 65.1%. With EUCAST breakpoints, categorical agreement (CA) was achieved in 38% isolates. Major discordance (MD-false susceptibility/resistance) and minor discordance (mD-false categorization involving intermediate results) were observed in 10% and 57% A. baumannii, respectively. With FDA breakpoints, CA, MD and mD were observed in 44%, 16% and 47% isolates, respectively. Colistin resistance was 2.1%.The study highlights a high proportion of CRAB and several discordances between BMD and gradient test which may lead to inappropriate therapy.


Assuntos
Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Tigeciclina/farmacologia , Acinetobacter baumannii/isolamento & purificação , Península Balcânica/epidemiologia , Carbapenêmicos/farmacologia , Hospitalização , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana
13.
Arch Immunol Ther Exp (Warsz) ; 64(1): 19-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26362801

RESUMO

Interferons (IFNs) are cytokines released by host cells in response to the presence of pathogens or tumor cells. The aim of this review was to present the previously known and new findings about the role of interferons type I and II, and recently discovered type III in Mycobacterium tuberculosis (M. tuberculosis) infection control. Infection of various cell types with M. tuberculosis induce both IFN-α and IFN-ß synthesis. The majority of the studies support the findings that IFN type I actually promotes infection with M. tuberculosis. It has been well establish that IFN-γ has protective function against M. tuberculosis and the other mycobacteria and that the primary source of this cytokine are CD4(+) and CD8(+) T cells. Recently, it has been shown that also the innate lymphocytes, γδ T cells, natural killer (NK) T cells, and NK cells can also be the source of IFN-γ in response to mycobacterial infection. Several studies have shown that CD4(+) T cells protect mice against M. tuberculosis independently of IFN-γ. The balance between IFN-γ and different cytokines such as IL-10 and other Th2 cell cytokines is likely to influence disease outcome. Type I IFN appears to be detrimental through at least three separate, but overlapping, type I IFN-mediated mechanisms: induction of excessive apoptosis, specific suppression of Th1 and IFN-γ responses, and dampening of the immune response by strong IL-10 induction. Recently it has been found that M. tuberculosis infection in A549 lung epithelial cells stimulate up-regulation of IFN-λ genes in vitro. IFN-λs also have a role in modulation of Th1/Th2 response. IFN-λs are not essential for M. tuberculosis infection control, but can give some contribution in immune response to this pathogen.


Assuntos
Citocinas/imunologia , Interferon Tipo I/imunologia , Interferon gama/imunologia , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculose/imunologia , Animais , Apoptose , Regulação da Expressão Gênica/imunologia , Humanos , Imunomodulação , Camundongos , Equilíbrio Th1-Th2
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