SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, displays a corona-shaped layer of spikes which play a fundamental role in the infection process. Recent structural data suggest ...that the spikes possess orientational freedom and the ribonucleoproteins segregate into basketlike structures. How these structural features regulate the dynamic and mechanical behavior of the native virion are yet unknown. By imaging and mechanically manipulating individual, native SARS-CoV-2 virions with atomic force microscopy, here, we show that their surface displays a dynamic brush owing to the flexibility and rapid motion of the spikes. The virions are highly compliant and able to recover from drastic mechanical perturbations. Their global structure is remarkably temperature resistant, but the virion surface becomes progressively denuded of spikes upon thermal exposure. The dynamics and the mechanics of SARS-CoV-2 are likely to affect its stability and interactions.
The SARS-CoV-2 pandemic, which started in December 2019, has been posing significant challenges to the health care system worldwide. As the pandemic spreads with rapidly increasing number of positive ...cases, early diagnosis of infected patients is crucial to successfully limit the spread of the virus. Although the real-time reverse-transcription polymerase chain reaction (RT-qPCR) is the recommended laboratory method to diagnose COVID-19 infection, many factors such as availability of laboratory equipment, reagents and trained personnel affect the use of time-consuming molecular techniques. To facilitate on-the-spot diagnosis of COVID-19, SARS-CoV-2 rapid antigen tests were developed by several different manufacturers. The evaluation of such rapid tests is particularly important due to the recent unanimous agreement by the European Commission Member States on a recommendation setting out a framework for the use of antigen rapid tests that contains a list of the mutually recognized assays and the basis of independent validation protocols. To evaluate the on-field performance of ten commercially available SARS-CoV-2 antigen rapid tests (CLINITEST Rapid COVID-19 Antigen Test, GenBody COVID-19 Antigen Test, GENEDIA W COVID-19 Ag Test, Healgen Coronavirus Antigen Rapid Test, Humasis COVID-19 Ag Test, VivaDiag SARS-CoV-2 Ag Rapid Test, Helix i-SARS-CoV-2 Ag Rapid Test, Roche SARS-CoV-2 Rapid Antigen Test, Abbot COVID-19 Ag Rapid Test and Vazyme SARS-CoV-2 Antigen Detection Kit) and compare with RT-qPCR as a reference method, the Hungarian National Public Health Center provided 1,597 antigen rapid tests to the National Ambulance Service, COVID-testing trucks and two hospitals treating COVID-19 patients. Sensitivity, specificity and accuracy were determined by performing the rapid test directly from nasopharyngeal swab samples of symptomatic individuals. For strongly positive samples (Ct < 25) sensitivities ranged between 66.7% and 100%, while for positive samples (Ct < 30) they gave a maximum sensitivity of 87.5%. The specificity of the tests was ranging between 79% to 100%. The results presented here are of high importance to the European Commission and also help governmental decision-making regarding the application of the proper rapid tests for screening different at-risk populations. Nonetheless, SARS-Cov-2 rapid tests play an important role in early and on-the-spot diagnosis of potentially infected individuals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Wastewater based epidemiology is a potential early warning tool for the detection of COVID-19 outbreak. Sewage surveillance for SARS-CoV-2 RNA was introduced in Hungary after the successful ...containment of the first wave of the pandemic to forecast the resurge of infections. Three wastewater treatment plants servicing the entire population (1.8 million) of the capital, Budapest were sampled weekly. 24 h composite (n = 44) and grab samples (n = 21) were concentrated by an in-house flat sheet membrane ultrafiltration method. The efficiency and reproducibility of the method was comparable to those previously published. SARS-CoV-2 RNA was quantified using RT-qPCR of the N gene. The first positive signal in sewage was detected 2 weeks before the rise in case numbers. Viral concentration and volume-adjusted viral load correlated to the weekly new cases from the same week and the rolling 7-day average of active cases in the subsequent week. The correlation was more pronounced in the ascending phase of the outbreak, data was divergent once case numbers plateaued. Wastewater surveillance was found to be effective in predicting the second wave of the outbreak in Hungary. Data indicated that even relatively low frequency (weekly) sampling is useful and at the same time, cost effective tool in outbreak detection.
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•First study of SARS-CoV-2 in sewage in Hungary•Membrane ultrafiltration method was developed for virus concentration.•First detects of viral RNA in sewage preceded the resurge of cases by 2 weeks.•Viral load correlated to the number of weekly new and active cases•Correlation was more pronounced in the ascending phase of second wave.
The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: ...Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals.
Incidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 – incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day.
Between 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73–9.3/100 000 person-days and 0.04–0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%–70.1%) and 88.7% (95% CI 86.6%–90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%–89.4%) and 97.5% (95% CI 95.6%–98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16–44 years for all vaccines.
Our observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.
ICTV Virus Taxonomy Profile: Filoviridae Kuhn, Jens H; Amarasinghe, Gaya K; Basler, Christopher F ...
Journal of general virology,
06/2019, Letnik:
100, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Members of the family Filoviridae produce variously shaped, often filamentous, enveloped virions containing linear non-segmented, negative-sense RNA genomes of 15-19 kb. Several filoviruses (e.g., ...Ebola virus) are pathogenic for humans and are highly virulent. Several filoviruses infect bats (e.g., Marburg virus), whereas the hosts of most other filoviruses are unknown. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on Filoviridae, which is available at www.ictv.global/report/filoviridae.
Diphyllin (1) and justicidin B (2) are arylnaphthalene lignans with antiviral and antiproliferative effects. Compound 1 is also known as an effective inhibitor of the Severe Acute Respiratory ...Syndrome Coronavirus 2 (SARS-CoV-2). To evaluate the in vitro antiviral and cytotoxic potency of both lignans in SARS-CoV-2 -infected cells and various cancer cell lines, respectively, 1 and 2 were isolated from the underground organs of Linum austriacum and Linum perenne. Two previously undescribed arylnaphthalene lignans, denominated linadiacin A and B (3 and 4), were also isolated and identified. In acidic media, 3 was converted by a two-step reaction into 2 via the intermediate 4. Optimum acid treatment conditions were determined to isolate lignans by one-step preparative high-performance liquid chromatography (HPLC). The results of the conversion, HPLC-tandem mass spectrometry, nuclear magnetic resonance spectroscopy, and molecular modeling studies allowed complete structure analysis. Compounds 1 and 2 were the most effective against SARS-CoV-2 with a 3-log reduction in the viral copy number at a 12.5 μM concentration. Ten human cancer cell lines showed sensitivity to at least one of the isolated lignans.
Abstract
Wastewater-based epidemiology (WBE) is a recognised tool for tracking community transmission of COVID-19. From the second half of 2020, the emergence of new, highly infective, more ...pathogenic or vaccine-escape SARS-CoV-2 variants is the major public health concern. Variant analysis in sewage might assist the early detection of new mutations. Weekly raw sewage samples from 22 wastewater treatment plants (WWTPs) in Hungary (representing 40% of the population) were analysed between December 2020 and March 2021 for signature mutations N501Y and del H69/V70 of B.1.1.7 lineage by melting point genotyping and RT-digital droplet PCR (RT-ddPCR). The latter method proved to be more efficient in parallel detection of different variants and also provides quantitative information. Wastewater surveillance indicated that the B.1.1.7 variant first emerged in Budapest in early January 2021 and rapidly became dominant in the entire country. Results are in close agreement with the available clinical data (Pearson's correlation coefficient, R = 0.9153). RT-ddPCR was confirmed to be a reliable tool for tracking emerging variant ratios in wastewaters. It is a rapid and cost-effective method compared to whole-genome sequencing, but only applicable for the detection of known mutations. Efficient variant surveillance might require the combination of multiple methods.
(1) Background: Crimean–Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease endemic in Africa, Asia, the Middle East, and the Balkan and Mediterranean regions of Europe. Although no ...human CCHF cases have been reported, based on vector presence, serological evidence among small vertebrates, and the general human population, Hungary lies within high evidence consensus for potential CCHF introduction and future human infection. Thus, the aim of our pilot serosurvey was to assess CCHF seropositivity among cattle and sheep as indicator animals for virus circulation in the country. (2) Methods: In total, 1905 serum samples taken from free-range cattle and sheep in 2017 were tested for the presence of anti-CCHF virus IgG antibodies using commercial ELISA and commercial and in-house immunofluorescent assays. (3) Results: We found a total of eleven reactive samples (0.58%) from five administrative districts of Hungary comprising 8 cattle and 3 sheep. The most affected regions were the south–central and northwestern parts of the country. (4) Conclusions: Based on these results, more extended surveillance is advised, especially in the affected areas, and there should be greater awareness among clinicians and other high-risk populations of the emerging threat of CCHF in Hungary and Central Europe.
One of the main hallmarks of tuberculosis (TB) is the ability of the causative agent to transform into a stage of dormancy and the capability of long persistence in the host phagocytes. It is ...believed that approximately one-third of the population of the world is latently infected with
(
), and 5%-10% of these individuals can develop clinical manifestations of active TB even decades after the initial infection. In this latent, intracellular form, the
is shielded by an extremely robust cell wall and becomes phenotypically resistant to most antituberculars. Therefore, there is a clear rationale to develop novel compounds or carrier-conjugated constructs of existing drugs that are effective against the intracellular form of the bacilli. In this paper, we describe an experimental road map to define optimal candidates against intracellular
and potential compounds effective in the therapy of latent TB. To validate our approach, isoniazid, a first-line antitubercular drug was employed, which is active against extracellular
in the submicromolar range, but ineffective against the intracellular form of the bacteria. Cationic peptide conjugates of isoniazid were synthesized and employed to study the host-directed drug delivery. To measure the intracellular killing activity of the compounds,
-infected MonoMac-6 human monocytic cells were utilized. We have assessed the antitubercular activity, cytotoxicity, membrane interactions in combination with internalization efficacy, localization, and penetration ability on interface and tissue-mimicking 3D models. Based on these
data, most active compounds were further evaluated
in a murine model of TB. Intraperitoneal infectious route was employed to induce a course of slowly progressive and systemic disease. The well-being of the animals, monitored by the body weight, allows a prolonged experimental setup and provides a great opportunity to test the long-term activity of the drug candidates. Having shown the great potency of this simple and suitable experimental design for antimicrobial research, the proposed novel assay platform could be used in the future to develop further innovative and highly effective antituberculars.
A comparative phytochemical study on the phenylethanoid glycoside (PhEG) composition of the underground organs of three
species (
,
and
) and that of the fruit wall and seed parts of
and
fruits was ...performed. The leaves of these
species and six cultivars of the hybrid
were also analyzed, demonstrating the tissue-specific accumulation and decomposition of PhEGs. Our analyses confirmed the significance of selected tissues as new and abundant sources of these valuable natural compounds. The optimized heat treatment of tissues containing high amounts of the PhEG plantamajoside (PM) or forsythoside A (FA), which was performed in distilled water, resulted in their characteristic isomerizations. In addition to PM and FA, high amounts of the isomerization products could also be isolated after heat treatment. The isomerization mechanisms were elucidated by molecular modeling, and the structures of PhEGs were identified by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HR-MS) techniques, also confirming the possibility of discriminating regioisomeric PhEGs by tandem MS. The PhEGs showed no cytostatic activity in non-human primate Vero E6 cells, supporting their safe use as natural medicines and allowing their antiviral potency to be tested.
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