| 1. |
- King, Carina, et al.
(författare)
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COVID-19—a very visible pandemic
- 2020
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 396:10248, s. 15-15
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Adel, Amany, et al.
(författare)
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Genetic Variations among Different Variants of G1-like Avian Influenza H9N2 Viruses and Their Pathogenicity in Chickens
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Since it was first discovered, the low pathogenic avian influenza (LPAI) H9N2 subtype has established linages infecting the poultry population globally and has become one of the most prevalent influenza subtypes in domestic poultry. Several different variants and genotypes of LPAI H9N2 viruses have been reported in Egypt, but little is known about their pathogenicity and how they have evolved. In this study, four different Egyptian LPAI H9N2 viruses were genetically and antigenically characterized and compared to representative H9N2 viruses from G1 lineage. Furthermore, the pathogenicity of three genetically distinct Egyptian LPAI H9N2 viruses was assessed by experimental infection in chickens. Whole-genome sequencing revealed that the H9N2 virus of the Egy-2 G1-B lineage (pigeon-like) has become the dominant circulating H9N2 genotype in Egypt since 2016. Considerable variation in virus shedding at day 7 post-infections was detected in infected chickens, but no significant difference in pathogenicity was found between the infected groups. The rapid spread and emergence of new genotypes of the influenza viruses pinpoint the importance of continuous surveillance for the detection of novel reassortant viruses, as well as monitoring the viral evolution.
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| 3. |
- Akaberi, Dario, et al.
(författare)
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Identification of a C2-symmetric diol based human immunodeficiency virus protease inhibitor targeting Zika virus NS2B-NS3 protease
- 2020
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Ingår i: Journal of Biomolecular Structure and Dynamics. - : Informa UK Limited. - 0739-1102 .- 1538-0254. ; 38:18, s. 5526-5536
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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.
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| 4. |
- Akaberi, Dario, 1989-
(författare)
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Identification of protease inhibitors against Flaviviruses and Coronaviruses
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vector-borne flaviviruses and coronaviruses of zoonotic origins are important human pathogens and represent a serious threat to public health worldwide. Flaviviruses can be found on all continents, apart from Antarctica, where they are transmitted by arthropod vectors causing millions of infections every year. While most of the infections are mild or asymptomatic, flaviviruses like dengue and yellow fever viruses can cause potentially lethal hemorrhagic fever and shock syndrome. Neurotropic flaviviruses like West Nile, Japanese encephalitis, and Tick-borne encephalitis (TBEV) can cause meningoencephalitis with long-term symptoms. Coronaviruses, and in particular betacoronaviruses of zoonotic origin like SARS (2003) and MERS (2012), have been periodically emerging since the early 2000s causing outbreaks of severe respiratory syndrome. The latest example is SARS-CoV-2 that after causing a cluster of infection in the Chinese city of Wuhan, spread all over the world causing at present over 6.9 million deaths. Although vaccines are essential in preventing infections or severe disease and hospitalization in the case of SARS-CoV-2, antivirals represent an extremely valuable tool for treatment and prevention of current and future flavivirus and coronavirus infections. In the work presented in this thesis we have used a combination of in silico and in vitro techniques to identify and test the activity of potential inhibitors of viral proteases. In our first study (paper 1) we unexpectedly identified an HIV protease inhibitor with in vitro activity against ZIKV NS2B-NS3 protease. The inhibitor was identified by virtual screening of a library of known protease inhibitors, evaluated by molecular dynamics simulation and finally tested against recombinant ZIKV protease using a FRET-based enzymatic assay. The same combination of molecular docking and molecular dynamics simulations were also used to correctly predict the activity of a known pan-Flavivirus protease inhibitor against TBEV protease (paper 2). As a result, we were the first to report peptide-based compounds with in vitro activity against TBEV. After the outbreak of the COVID-19 we switched our attention to SARS-CoV-2. We first tested the inhibitory effect of the broad-spectrum antiviral nitric oxide (NO) and found that the NO-releasing compound SNAP had a dose dependent inhibitory effect on SARS-CoV-2 replication in cell-based assays (paper 3). We speculated that SNAP could inhibit SARS-COV-2 protease by trans-nitration of the catalytic Cys145 of SARS-CoV-2 main protease and found that SNAP had a dose dependent inhibitory effect on recombinant SARS-CoV-2 Mpro protease activity in an in vitro enzymatic assay. In our last study (paper 4) we identified a new class of potent SARS-CoV-2 protease inhibitors through the affinity screening of DNA-encoded-chemical libraries containing 4.2 billion compounds. The identified compounds inhibited recombinant SARS-CoV-2 protease with IC50 as low as 25 nM and had a dose dependent antiviral effect in the low micromolar range in infected Calu-3 and Caco-2 cell lines.
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| 5. |
- Akaberi, Dario, 1989-, et al.
(författare)
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Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
- 2020
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Ingår i: Redox Biology. - : Elsevier. - 2213-2317. ; 37
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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.
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| 6. |
- Akaberi, Dario, et al.
(författare)
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Targeting the NS2B-NS3 protease of tick-borne encephalitis virus with pan-flaviviral protease inhibitors
- 2021
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Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 190
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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.
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| 7. |
- Albinsson, Bo, et al.
(författare)
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Multi laboratory evaluation of ReaScan TBE IgM rapid test, 2016 to 2017
- 2020
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Ingår i: Eurosurveillance. - : EUR CENTRE DIS PREVENTION & CONTROL. - 1025-496X .- 1560-7917. ; 25:12, s. 27-36
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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.
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| 8. |
- Albinsson, Bo, et al.
(författare)
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Seroprevalence of tick-borne encephalitis virus and vaccination coverage of tick-borne encephalitis, Sweden, 2018 to 2019
- 2024
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Ingår i: Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. - : European Centre for Disease Control and Prevention (ECDC). - 1560-7917 .- 1025-496X. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn Sweden, information on seroprevalence of tick-borne encephalitis virus (TBEV) in the population, including vaccination coverage and infection, is scattered. This is largely due to the absence of a national tick-borne encephalitis (TBE) vaccination registry, scarcity of previous serological studies and use of serological methods not distinguishing between antibodies induced by vaccination and infection. Furthermore, the number of notified TBE cases in Sweden has continued to increase in recent years despite increased vaccination.AimThe aim was to estimate the TBEV seroprevalence in Sweden.MethodsIn 2018 and 2019, 2,700 serum samples from blood donors in nine Swedish regions were analysed using a serological method that can distinguish antibodies induced by vaccination from antibodies elicited by infection. The regions were chosen to reflect differences in notified TBE incidence.ResultsThe overall seroprevalence varied from 9.7% (95% confidence interval (CI): 6.6-13.6%) to 64.0% (95% CI: 58.3-69.4%) between regions. The proportion of vaccinated individuals ranged from 8.7% (95% CI: 5.8-12.6) to 57.0% (95% CI: 51.2-62.6) and of infected from 1.0% (95% CI: 0.2-3.0) to 7.0% (95% CI: 4.5-10.7). Thus, more than 160,000 and 1,600,000 individuals could have been infected by TBEV and vaccinated against TBE, respectively. The mean manifestation index was 3.1%.ConclusionA difference was observed between low- and high-incidence TBE regions, on the overall TBEV seroprevalence and when separated into vaccinated and infected individuals. The estimated incidence and manifestation index argue that a large proportion of TBEV infections are not diagnosed.
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| 9. |
- Amer, Fatma, et al.
(författare)
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Temporal Dynamics of Influenza A(H5N1) Subtype before and after the Emergence of H5N8
- 2021
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 13:8
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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.
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| 10. |
- Bergman, Alexander, et al.
(författare)
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Sindbis Virus Infection in Non-Blood-Fed Hibernating Culex pipiens Mosquitoes in Sweden
- 2020
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 12:12
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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.
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