| 1. |
- King, Carina, et al.
(författare)
-
COVID-19—a very visible pandemic
- 2020
-
Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 396:10248, s. 15-15
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Akaberi, Dario, et al.
(författare)
-
Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease
- 2020
-
Ingår i: Journal of Biomolecular Structure and Dynamics. - : Informa UK Limited. - 0739-1102 .- 1538-0254. ; 38:18, s. 5526-5536
-
Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) is an emerging mosquito-borne flavivirus and infection by ZIKV Asian lineage is known to cause fetal brain anomalies and Guillain-Barrés syndrome. The WHO declared ZIKV a global public health emergency in 2016. However, currently neither vaccines nor antiviral prophylaxis/treatments are available. In this study, we report the identification of a C2-symmetric diol-based Human immunodeficiency virus type-1 (HIV) protease inhibitor active against ZIKV NS2B-NS3 protease. The compound, referred to as 9b, was identified by in silico screening of a library of 6265 protease inhibitors. Molecular dynamics (MD) simulation studies revealed that compound 9b formed a stable complex with ZIKV protease. Interaction analysis of compound 9b's binding pose from the cluster analysis of MD simulations trajectories predicted that 9b mostly interacted with ZIKV NS3. Although designed as an aspartyl protease inhibitor, compound 9b was found to inhibit ZIKV serine protease in vitro with IC50 = 143.25 ± 5.45 µM, in line with the in silico results. Additionally, linear interaction energy method (LIE) was used to estimate binding affinities of compounds 9b and 86 (a known panflavivirus peptide hybrid with IC50 = 1.64 ± 0.015 µM against ZIKV protease). The LIE method correctly predicted the binding affinity of compound 86 to be lower than that of 9b, proving to be superior to the molecular docking methods in scoring and ranking compounds. Since most of the reported ZIKV protease inhibitors are positively charged peptide-hybrids, with our without electrophilic warheads, compound 9b represents a less polar and more drug-like non-peptide hit compound useful for further optimization.Communicated by Ramaswamy Sarma.
|
|
| 3. |
- Akaberi, Dario, 1989-, et al.
(författare)
-
Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
- 2020
-
Ingår i: Redox Biology. - : Elsevier. - 2213-2317. ; 37
-
Tidskriftsartikel (refereegranskat)abstract
- The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 μM and 400 μM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.
|
|
| 4. |
- Akaberi, Dario, et al.
(författare)
-
Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors
- 2021
-
Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 190
-
Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a severe neurological disorder caused by tick-borne encephalitis virus (TBEV), a member of the Flavivirus genus. Currently, two vaccines are available in Europe against TBEV. However, TBE cases have been rising in Sweden for the past twenty years, and thousands of cases are reported in Europe, emphasizing the need for antiviral treatments against this virus. The NS2B-NS3 protease is essential for flaviviral life cycle and has been studied as a target for the design of inhibitors against several well-known flaviviruses, but not TBEV. In the present study, Compound 86, a known tripeptidic inhibitor of dengue (DENV), West Nile (WNV) and Zika (ZIKV) proteases, was predicted to be active against TBEV protease using a combination of in silico techniques. Further, Compound 86 was found to inhibit recombinant TBEV protease with an IC50 = 0.92 mu M in the in vitro enzymatic assay. Additionally, two more peptidic analogues were synthetized and they displayed inhibitory activities against both TBEV and ZIKV proteases. In particular, Compound 104 inhibited ZIKV protease with an IC50 = 0.25 mu M. These compounds represent the first reported inhibitors of TBEV protease to date and provides valuable information for the further development of TBEV as well as pan-flavivirus protease inhibitors.
|
|
| 5. |
- Albinsson, Bo, et al.
(författare)
-
Multi laboratory evaluation of ReaScan TBE IgM rapid test, 2016 to 2017
- 2020
-
Ingår i: Eurosurveillance. - : EUR CENTRE DIS PREVENTION & CONTROL. - 1025-496X .- 1560-7917. ; 25:12, s. 27-36
-
Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a potentially severe neurological disease caused by TBE virus (TBEV). In Europe and Asia, TBEV infection has become a growing public health concern and requires fast and specific detection. Aim: In this observational study, we evaluated a rapid TBE IgM test, ReaScan TBE, for usage in a clinical laboratory setting. Methods: Patient sera found negative or positive for TBEV by serological and/or molecular methods in diagnostic laboratories of five European countries endemic for TBEV (Estonia, Finland, Slovenia, the Netherlands and Sweden) were used to assess the sensitivity and specificity of the test. The patients' diagnoses were based on other commercial or quality assured in-house assays, i.e. each laboratory's conventional routine methods. For specificity analysis, serum samples from patients with infections known to cause problems in serology were employed. These samples tested positive for e.g. Epstein-Barr virus, cytomegalovirus and Anaplasma phagocytophilum, or for flaviviruses other than TBEV, i.e. dengue, Japanese encephalitis, West Nile and Zika viruses. Samples from individuals vaccinated against flaviviruses other than TBEV were also included. Altogether, 172 serum samples from patients with acute TBE and 306 TBE IgM negative samples were analysed. Results: Compared with each laboratory's conventional methods, the tested assay had similar sensitivity and specificity (99.4% and 97.7%, respectively). Samples containing potentially interfering antibodies did not cause specificity problems. Conclusion: Regarding diagnosis of acute TBEV infections, ReaScan TBE offers rapid and convenient complementary IgM detection. If used as a stand-alone, it can provide preliminary results in a laboratory or point of care setting.
|
|
| 6. |
- Amer, Fatma, et al.
(författare)
-
Temporal Dynamics of Influenza A(H5N1) Subtype before and after the Emergence of H5N8
- 2021
-
Ingår i: Viruses. - : MDPI. - 1999-4915. ; 13:8
-
Tidskriftsartikel (refereegranskat)abstract
- Highly pathogenic avian influenza (HPAI) viruses continue to circulate worldwide, causing numerous outbreaks among bird species and severe public health concerns. H5N1 and H5N8 are the two most fundamental HPAI subtypes detected in birds in the last two decades. The two viruses may compete with each other while sharing the same host population and, thus, suppress the spread of one of the viruses. In this study, we performed a statistical analysis to investigate the temporal correlation of the HPAI H5N1 and HPAI H5N8 subtypes using globally reported data in 2015-2020. This was joined with an in-depth analysis using data generated via our national surveillance program in Egypt. A total of 6412 outbreaks were reported worldwide during this period, with 39% (2529) as H5N1 and 61% (3883) as H5N8. In Egypt, 65% of positive cases were found in backyards, while only 12% were found in farms and 23% in live bird markets. Overall, our findings depict a trade-off between the number of positive H5N1 and H5N8 samples around early 2017, which is suggestive of the potential replacement between the two subtypes. Further research is still required to elucidate the underpinning mechanisms of this competitive dynamic. This, in turn, will implicate the design of effective strategies for disease control.
|
|
| 7. |
- Bergman, Alexander, et al.
(författare)
-
Sindbis Virus Infection in Non-Blood-Fed Hibernating Culex pipiens Mosquitoes in Sweden
- 2020
-
Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- A crucial, but unresolved question concerning mosquito-borne virus transmission is how these viruses can remain endemic in regions where the transmission is halted for long periods of time, due to mosquito inactivity in, e.g., winter. In northern Europe, Sindbis virus (SINV) (genus alphavirus, Togaviridae) is transmitted among birds by Culex mosquitoes during the summer, with occasional symptomatic infections occurring in humans. In winter 2018-19, we sampled hibernating Culex spp females in a SINV endemic region in Sweden and assessed them individually for SINV infection status, blood-feeding status, and species. The results showed that 35 out of the 767 collected mosquitoes were infected by SINV, i.e., an infection rate of 4.6%. The vast majority of the collected mosquitoes had not previously blood-fed (98.4%) and were of the species Cx. pipiens (99.5%). This is the first study of SINV overwintering, and it concludes that SINV can be commonly found in the hibernating Cx. pipiens population in an endemic region in Sweden, and that these mosquitoes become infected through other means besides blood-feeding. Further studies on mosquito ecology and viral interactions are needed to elucidate the mechanisms of the persistence of these viruses over winter.
|
|
| 8. |
- Bucardo, Filemón, et al.
(författare)
-
Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor a Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua
- 2021
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 223:2, s. 278-286
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundChikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya.MethodsTo test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays.ResultsAfter adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively).ConclusionThis study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.
|
|
| 9. |
- Chen, Xiaoping, et al.
(författare)
-
Risk factors for the delayed viral clearance in COVID‐19 patients
- 2021
-
Ingår i: The Journal of Clinical Hypertension. - : John Wiley & Sons. - 1524-6175 .- 1751-7176. ; 23:8, s. 1483-1489
-
Tidskriftsartikel (refereegranskat)abstract
- Comorbidities are important for the disease outcome of COVID-19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID-19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID-19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan-Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS-CoV-2 virus clearance, however, the use of Angiotensin-Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID-19 patients.
|
|
| 10. |
- Hassan, Mohammad Mahmudul, et al.
(författare)
-
Residual antimicrobial agents in food originating from animals
- 2021
-
Ingår i: Trends in Food Science & Technology. - : Elsevier. - 0924-2244 .- 1879-3053. ; 111, s. 141-150
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The agricultural food products industry in Bangladesh depends on utilizing antimicrobials indiscriminately as growth promoters and for controlling infectious diseases. Thus, there is always a risk of antimicrobial agent accumulation in food sources that originate from agricultural production.Methods: In the present study, we collected data from published articles between January, 2013 and December, 2019 on antimicrobial residues in human food sources such as meat, milk, eggs, and fishes.Results: Liver contained the highest percentage of antimicrobial residues (74%; 95% CI: 59.66?85.37) against the in vitro enteric pathogen Escherichia coli in layer chickens. Similar results were demonstrated in liver (68%; 95% CI: 53.30?80.48) and kidney (66%, 95% CI: 51.23?78.79) of layer chickens against Bacillus cereus and Bacillus subtilis. Amongst all antibiotics, the highest concentrations of ciprofloxacin were detected in kidney (48.57%; 95% CI: 31.38?66.01), followed by liver (47.56; 95% CI: 40.88?54.30) of broiler chickens. Ciprofloxacin was also present in liver (46.15%; 95% CI: 33.70?58.96) of layer chickens. The percentage of ciprofloxacin in thigh and breast meat in broiler bird were 41.54% (95% CI: 34.54?48.79) and 37.95% (95% CI: 31.11?45.15) respectively. Enrofloxacin was the second most dominant antimicrobial agent and was present in the liver of both types of poultry (Broiler and Layer chickens: 41.54%; 95% CI: 29.44?54.4 and 437.33%; 95% CI: 30.99?44.01). The prevalence rates of enrofloxacin in thigh and breast meat of broiler chickens were 24.10% (95% CI: 18.28?30.73) and 20.51% (95% CI: 15.08?26.87), respectively. Tetracycline, a commonly used antibiotic in livestock, was present in the liver (49.23%; 95% CI: 36.60?61.93) of layer chickens. In case of aquaculture food products, the highest amount of amoxicillin (683.2 mg/kg) was detected in Tilapia fish (Oreochromis niloticus), followed by 584.4 mg/kg in climbing perch (Anabas testudineus) and 555.6 mg/kg in Rui fish (Labeo rohita). Among the five types of fishes, Rui fish (0.000515 mg/kg) contained the highest concentrations of chloramphenicol antibiotic residues.Conclusions: The presence of antimicrobial residues in meat, milk, egg, and fish is a serious public health threat due to the potential induction of antimicrobial resistance. It can negatively impact the food supply chain, especially with the current strain that it is already facing with the current COVID-19 pandemic. The findings of the present study highlight the ongoing risk of residual antimicrobial agents in food of animal origin in Bangladesh and countries with similar practices. This can draw the attention of public health officials to propose plans to mitigate or stop this practice.
|
|
