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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
311

COVID-19 in German Competitive Sports: Protocol for a Prospective Multicenter Cohort Study (CoSmo-S)

Niess, Andreas Michael, Widmann, Manuel, Gaidai, Roman, Gölz, Christian, Schubert, Isabel, Castillo, Katty, Sachs, Jan Philipp, Bizjak, Daniel, Vollrath, Shirin, Wimbauer, Fritz, Vogel, Azin, Keller, Karsten, Burgstahler, Christof, Quermann, Anne, Kerling, Arno, Schneider, Gerald, Zacher, Jonas, Diebold, Katharina, Grummt, Maximilian, Beckendorf, Claudia, Buitenhuis, Johannes, Egger, Florian, Venhorst, Andreas, Morath, Oliver, Barsch, Friedrich, Mellwig, Klaus-Peter, Oesterschlink, Julian, Wüstenfeld, Jan, Predel, Hans-Georg, Deibert, Peter, Friedmann-Bette, Birgit, Mayer, Frank, Hirschmüller, Anja, Halle, Martin, Steinacker, Jürgen Michael, Wolfarth, Bernd, Meyer, Tim, Böttinger, Erwin, Flechtner-Mors, Marion, Bloch, Wilhelm, Haller, Bernhard, Roecker, Kai, Reinsberger, Claus 25 January 2024 (has links)
Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARSCoV- 2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level.
312

IFN-γ Increases the Expression of SARS-CoV-2 Receptors on Vero E6 cells

Madabattula, Bindu Madhavi January 2022 (has links)
No description available.
313

Selection and Validation of siRNAs Preventing Uptake and Replication of SARS-CoV-2

Friedrich, Maik, Pfeifer, Gabriele, Binder, Stefanie, Aigner, Achim, Vollmer Barbosa, Philippe, Makert, Gustavo R., Fertey, Jasmin, Ulbert, Sebastian, Bodem, Jochen, König, Eva-Maria, Geiger, Nina, Schambach, Axel, Schilling, Erik, Buschmann, Tilo, Hauschildt, Sunna, Koehl, Ulrike, Sewald, Katherina 03 April 2023 (has links)
In 2019, the novel highly infectious severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) outbreak rapidly led to a global pandemic with more than 346 million confirmed cases worldwide, resulting in 5.5 million associated deaths (January 2022). Entry of all SARS-CoV-2 variants is mediated by the cellular angisin-converting enzyme 2 (ACE2). The virus abundantly replicates in the epithelia of the upper respiratory tract. Beyond vaccines for immunization, there is an imminent need for novel treatment options in COVID-19 patients. So far, only a few drugs have found their way into the clinics, often withmodest success. Specific gene silencing based on small interfering RNA (siRNA) has emerged as a promising strategy for therapeutic intervention, preventing/limiting SARS-CoV-2 entry into host cells or interfering with viral replication. Here, we pursued both strategies. We designed and screened nine siRNAs (siA1-9) targeting the viral entry receptor ACE2. SiA1, (siRNA against exon1 of ACE2 mRNA) was most efficient, with up to 90% knockdown of the ACE2 mRNA and protein for at least six days. In vitro, siA1 application was found to protect Vero E6 and Huh-7 cells from infectionwith SARS-CoV-2 with an up to ~92% reduction of the viral burden indicating that the treatment targets both the endosomal and the viral entry at the cytoplasmic membrane. Since the RNAencoded genome makes SARS-CoV-2 vulnerable to RNA interference (RNAi), we designed and analysed eight siRNAs (siV1-8) directly targeting the Orf1a/b region of the SARS-CoV-2 RNA genome, encoding for non-structural proteins (nsp). As a significant hallmark of this study, we identified siV1 (siRNA against leader protein of SARS-CoV-2), which targets the nsp1- encoding sequence (a.k.a. ‘host shutoff factor’) as particularly efficient. SiV1 inhibited SARSCoV- 2 replication in Vero E6 or Huh-7 cells by more than 99% or 97%, respectively. It neither led to toxic effects nor induced type I or III interferon production. Of note, sequence analyses revealed the target sequence of siV1 to be highly conserved in SARS-CoV-2 variants. Thus, our results identify the direct targeting of the viral RNA genome (ORF1a/b) by siRNAs as highly efficient and introduce siV1 as a particularly promising drug candidate for therapeutic intervention.
314

Optimierung und Validierung eines SARS-CoV-2-N IgG Antikörper ELISA

Schnurra, Carolin 04 January 2024 (has links)
Die neuartige Infektionskrankheit Covid-19 breitet sich seit Dezember 2019 von Wuhan, China, in zahlreiche Länder aller Kontinente aus. Durch die rasche Verbreitung der Viruserkrankung und die schnell steigende Zahl an infizierten Personen, rief die WHO im Januar 2020 die „Gesundheitliche Notlage internationaler Tragweite“ aus. Im März desselben Jahres wurde die Situation als Pandemie deklariert. Die Infektionskrankheit wird durch das SARS-CoV-2 hervorgerufen, ein Vertreter aus der Gattung der Betacoronaviren, dessen Genom durch einzelsträngige RNA positiver Polarität (ssRNA) gekennzeichnet ist. Ein zoonotischer Ursprung des Virus aus Fledermäusen wird derzeit aufgrund hoher genetischer Übereinstimmungen als wahrscheinlichste initiale Quelle betrachtet. Die Transmission des SARS-CoV-2 erfolgt über die respiratorische Aufnahme von virushaltigem Aerosol und ruft Symptome wie Husten, Fieber, Geschmacks- und Geruchsstörungen sowie bei schwerem Verlauf auch Pneumonien mit beatmungspflichtigem ARDS (Acute Respiratory Distress Syndrome) hervor. Eine spezifische Therapie für Covid-19 ist bisher nicht etabliert, jedoch sind supportive Maßnahmen sinnvoll, der Einsatz von Remdesivir von der Europäischen Arzneimittel-Agentur zugelassen und die Verwendung von systemischen Kortikosteroiden von der WHO empfohlen. Um die Basisreproduktionszahl für das SARS-CoV-2 gering zu halten, sind infektionspräventive Maßnahmen wie Mund-Nase-Bedeckung, Mindestabstand, regelmäßiger Luftaustausch und das strenge Einhalten von Hygieneregeln wirksam. Die ersten Impfstoffe für die Viruserkrankung Covid-19 stehen seit Dezember 2020 bereit. Da die Vakzine bislang begrenzt zur Verfügung stehen, ist eine frühzeitige Diagnostik und die Nachverfolgung des Infektionsgeschehens weiterhin von großer Bedeutung. Der direkte Erregernachweis des SARS-CoV-2 erfolgt durch einen Nasen-Rachen-Abstrich, der mittels RT-PCR auf replizierendes Virusgenom untersucht wird. Für die Erfassung der asymptomatisch bzw. subklinisch infizierten Personen sind neben dem Antigen-Schnelltest auch serologische Nachweisverfahren notwendig, um die reale Ausbreitung des SARS-CoV-2 nachvollziehen zu können. Ziel dieser Arbeit war es, durch zahlreiche Optimierungen ein valides Protokoll für einen SARS-CoV-2-N IgG Antikörper ELISA zu etablieren. Der Test sollte einen qualitativen Nachweis zur Detektion der SARS-CoV-2-Immunantwort gegen das Nukleokapsidprotein des Virus möglich machen. Die in das Protokoll aufgenommenen Optimierungen umfassen u. a. die Konzentration des verwendeten Antigens N-MBP, die Zusammensetzung der Beschichtungs- und Blocklösung, die Probenvolumina, die Verdünnung des Sekundärantikörpers und die Zeit der Substratinkubation für die Farbentwicklung. Für das Protokoll des SARS-CoV-2-N IgG Antikörper ELISA wurde ein Kalibrator entwickelt, um einen normierten Grenzwert für Seropositivität festlegen zu können und ein Antikörper-Konzentrationsstandard etabliert, um die Ergebnisse des Immunassays auch quantitativ interpretieren zu können. Zur Validierung des SARS-CoV-2-N IgG Antikörper ELISA wurden 73 Covid-19-Seren von Probanden mit zuvor positivem RT-PCR Testergebnis und 180 Negativkontrollseren bzw. -plasmen verwendet. Die Covid-19-Patienten zeigten eine milde bis moderate Erkrankung oder einen asymptomatischen Infektionsverlauf. Die Covid-19-Seren wurden 2 - 3 Wochen (n = 25) oder über 4 Wochen (n = 48) nach Symptombeginn bzw. positivem RNA-Test gewonnen. Die Spezifität des SARS-CoV-2-N IgG Antikörpertests betrug 99,44 % und die Sensitivität wurde mit 80,82 % ermittelt. Nach 2 - 3 Wochen entnommene Covid-19-Seren wurden dabei mit einer Sensitivität von 80,0 % und mehr als 4 Wochen nach Diagnosestellung gewonnene Seren mit einer Positivrate von 81,3 % erkannt. Weiterhin wurde die Empfindlichkeit des In-house ELISA in einer prospektiven diagnostischen Studie mit der Sensitivität von sieben kommerziellen Nukleokapsid- oder S-Glykoprotein-basierten Antikörpertests verglichen, um den Nutzen der Tests für den klinischen Einsatz bewerten zu können. Die Sensitivitäten der Antikörperassays lagen bei 64,4 - 93,2 %. Die empfindlichsten Tests erkannten 95,8 - 100 % der über 4 Wochen nach Symptombeginn gewonnenen Covid-19-Seren als positiv. Seren, die 2 - 3 Wochen nach positivem RNA-Test entnommen wurden, wurden mit einer geringeren Sensitivität erkannt, was darauf hindeutet, dass der optimale Zeitpunkt für serologische Testungen später als 3 Wochen nach Ausbruch der Infektionskrankheit liegen sollte. Antikörpertests, die das Nukleokapsid- bzw. das S-Glykoprotein als Antigen verwendeten, zeigten vergleichbare Sensitivitätswerte auf. Dies bedeutet, dass sowohl N- als auch S-basierte Antiköpertests für die serologische Diagnostik geeignet sind. Nukleokapsidprotein und S-Glykoprotein-basierte Antikörperassays zeigten außerdem Unterschiede in der Detektion einer positiven oder negativen Immunreaktion bei den untersuchten Covid-19-Seren. Eine kombinierte Auswertung von seriellen Tests unter separater Verwendung beider Antigene könnte somit die Positivrate bei der Untersuchung von Covid-19-Seren steigern.:INHALTSVERZEICHNIS ABKÜRZUNGSVERZEICHNIS III 1 EINFÜHRUNG 1 1.1 SARS-CoV-2: Virale Struktur und Replikation 1 1.2 Covid-19: Pathogenese und Krankheitsbild 3 1.3 Epidemiologie und Herkunft 6 1.4 Diagnostik 8 1.5 Therapie 11 1.6 Prävention 12 1.7 Impfung 12 2 AUFGABENSTELLUNG 15 3 MATERIALIEN UND METHODEN 16 3.1 Materialien 16 3.1.1 Geräte 16 3.1.2 Chemikalien 16 3.1.3 Proteine 17 3.1.4 Seren 17 3.1.5 Immunoreagenzien 18 3.1.6 Sonstige Materialien 18 3.2 Methoden 18 3.2.1 Allgemein verwendete Lösungen 18 3.2.2 Ethikantrag 19 3.2.3 Probanden 19 3.2.4 Probenentnahme 20 3.2.5 Probenaufarbeitung 20 3.2.6 Nukleokapsidprotein (N) und Maltose-bindendes Protein (MBP) 20 3.2.7 Enzyme-Linked Immunosorbent Assay (ELISA) 22 3.2.8 Kommerzielle Antikörpertests 23 3.2.9 Auswertung und Statistik 24 4 ERGEBNISSE 28 4.1 Optimierung des SARS-CoV-2-N IgG Antikörper ELISA 28 4.1.1 Beschichtung mit Nukleokapsid-Fusionsprotein 28 4.1.2 Einfluss der Antigenkonzentration in der Beschichtungslösung 29 4.1.3 Einfluss der Auftauhäufigkeit des N-MBP-Antigens 31 4.1.4 Variation der Beschichtungslösung 33 4.1.5 Beschichtungs- und Probenvolumina 34 4.1.6 Blocklösung 35 4.1.7 Substratinkubationszeit 36 4.1.8 Sekundärantikörperverdünnung 38 4.1.9 Stabilisierung des Protokolls mit CANDOR®-Reagenzien 40 4.2 Validierung des SARS-CoV-2-N IgG Antikörper ELISA 42 4.2.1 Herstellung eines Kalibrators 42 4.2.2 Bestimmung der Sensitivität 44 4.2.3 Bestimmung der Spezifität 46 4.2.4 Herstellung eines Antikörper-Konzentrationsstandards 47 4.2.5 Intra-Assay und Inter-Assay-Variabilität 49 4.3 Protokoll des SARS-CoV-2-N IgG Antikörper ELISA 50 4.4 Vergleich der diagnostischen Sensitivität von SARS-CoV-2-Nukleoprotein- und Glykoprotein-basierten Antikörpertests 53 5 DISKUSSION 58 5.1 Ergebnisse der diagnostischen Validierungsstudie 58 5.2 Eignung und Verwendung des Nukleokapsidproteins als Antigen für den SARS-CoV-2 IgG Antikörper ELISA 61 5.3 Validität und Limitationen 62 5.4 Ausblick und Bedeutung des SARS-CoV-2-N IgG Antikörpertests 64 6 ZUSAMMENFASSUNG 67 LITERATURVERZEICHNIS 70 ANLAGEN 89 ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT 92 LEBENSLAUF 93 PUBLIKATIONSVERZEICHNIS 95 DANKSAGUNG 96
315

ANTIBIOTICS USE FOR TREATING HOSPITALIZED COVID-19 PATIENTS: A SYSTEMATIC REVIEW & META-ANALYSIS

Rabbi, Fazle January 2022 (has links)
ACKNOWLEDGEMENTS I would like to take this moment to extend my utmost appreciation for all the support provided by my supervisor, Dr. Russell de Souza. He assisted me along the way and ensured that I was always on the right path to achieve all my goals and checkpoints in every circumstance. I would also like to thank my committee for providing me with fantastic support: Ms. Laura Banfield for always being there to help solve any problem in this process, and Dr. Zain Chagla for providing a plethora of knowledge from the technical perspective of infectious disease and being so patient. Special thanks to Dr. Alexandra Mayhew for her support in our prevalence meta-analysis. Finally, I would like to thank my family, my wife, Dr. Sanjida Rowshan Anannya, for whom I am here today, and my parents, siblings, and in-laws; you are always there for me in every walk of life. You are why I have gotten to where I am today and are my daily inspiration. / Background: Bacteria is a major cause of many infectious diseases, and the treatment for these diseases is antibiotics designed to kill or subdue the growth of the bacteria. However, bacteria evolve, and if an antibiotic prescription is not the right antibiotic for the right patient at the right time with the correct dose and the right route, Antimicrobial Resistance (AMR) may result. During this pandemic, the use of antibiotics to treat hospitalized COVID-19 patients without any bacterial coinfection threatens the effectiveness of antibiotic treatment for current and future bacterial infections. Methods: A systematic search was conducted of the Embase, Medline, Web of Science, and Cochrane Library databases by generating search terms using the concepts of “COVID-19,” “Bacterial Coinfection,” “Secondary bacterial infection,” and “Antimicrobial resistance” to identify studies that reported the prevalence of antibiotic prescription for the treatment of COVID-19 in hospitalized patients with and without bacterial coinfection. The pooled estimate of the percentage of the total and confirmed appropriate antibiotic prescriptions provided to hospitalized COVID-19 patients was generated using a random effect meta-analysis with inverse variance weighting. Result: Of 157,623 participants from 29 studies included in our review, 67% (CI 64% to 71%, P<0.00001) were prescribed antibiotics, among which 80% (CI 76% to 83%, P<0.00001) prescriptions were given for the COVID-19 patients without any bacterial coinfections. The use of antibiotics varied during the pre-immunosuppressive period (before 16 June 2020) and post-immunosuppressive period of the pandemic and between the High-Income Countries and Upper and Lower Middle-Income Countries. Conclusion: This Systematic Review and Meta-analysis finds greater than expected use of antibiotics to treat hospitalized COVID-19 patients without bacterial coinfections, which can worsen AMR globally. Clear and concrete guidelines for the use of antibiotic prescriptions to treat COVID-19 patients, strict monitoring, and compliance with Antimicrobial Stewardship are needed to prevent over-prescription. / Thesis / Master in Advanced Studies (MAS) / Bacteria is a major cause of many infectious diseases. Before the discovery of Antibiotics in 1928, hundreds of thousands of people used to die due to infectious diseases caused by bacteria. While Antibiotics are essential to treat bacterial infectious diseases, overuse or misuse can accelerate Antibiotic Resistance, a phenomenon when bacteria change and/or develop the ability to escape the drugs designed to kill them. Self-medication, availability of antibiotics without a prescription, and inappropriate dosing of antibiotics can worsen the situation. During the COVID-19 pandemic, antibiotics were commonly prescribed as part of the treatment regime for COVID-19, even when a clear bacterial infection was not identified. In our Systematic Review and Meta-analysis, we aimed to see the frequency of antibiotic prescriptions to treat hospitalized COVID-19 patients without any bacterial coinfections.
316

Effekt och tolerabilitet av humant rekombinant lösligt ACE2 vid behandling av Covid-19 : En litteraturstudie baserad på effekten av humant rekombinant lösligt ACE2 vid behandling av sjukdomen Covid-19 samt läkemedlets tolerabilitet.

Baykal, Nevin January 2023 (has links)
No description available.
317

Effective Strategies for Preventing and Mitigating Emerging Viruses

Chuong, Christina 08 May 2023 (has links)
The world is grappling with an escalating risk of viral outbreaks of pandemic proportion, with zoonotic RNA viruses such as chikungunya virus (CHIKV) and SARS-CoV-2 posing significant threats to global health. Several environmental and evolutionary factors have fueled the emergence and spread of infection, creating a constant arms race against emerging pathogens. Current prevention and mitigation strategies are inadequate, necessitating tools to prevent and control viral infections; innovative strategies are needed in the pipeline to address significant challenges. CHIKV is a mosquito-borne virus that has caused millions of disease cases worldwide and is a reemerging threat with increasing potential to become endemic in the US. Currently, there are no licensed treatments available to protect against CHIK disease, making the development of a vaccine crucial. Live-attenuated vaccines (LAVs) have traditionally been a promising strategy due to their high immunogenicity and cost-effectiveness. However, concerns regarding adverse side effects and the potential for viral replication leading to pathogenic reversions or transmission into mosquitoes have limited their use. To that end, we have developed a new generation of safer vaccines by modifying the standard LAV platform through innovative attenuating strategies. Our dual-attenuated platform utilizes a previously developed chimera of CHIKV and the closely related Semliki Forest virus (SFV) as a vaccine backbone which expresses antiviral mouse cytokines IFN-γ or IL-21, as an additional mechanism to control infection. In several mouse models, both cytokine-expressing candidates showed reduced footpad swelling and minimal to no systemic replication or dissemination capacity compared to the parental vaccine post-vaccination. Importantly, these candidates conferred full protection from wildtype CHIK disease. Our IFNγ-expressing vaccine showed the most significant attenuation of viral replication. To understand the underlying mechanism, we identified three IFNγ-regulated antiviral genes (Gbp1/2 and Ido1) that were highly upregulated in 3T3 mouse fibroblasts post-infection with the IFN-γ-expressing candidate but not the parental backbone. To further investigate the role of these genes in restricting viral replication and enhance the clinical relevance of our vaccine platform, we redesigned our vaccine to express human IFNγ (hIFNγ) and performed viral growth kinetics in MRC5 human lung fibroblasts. Our vaccine showed reduced viral replication compared to controls and high expression of human GBP1/2/3 was observed post-infection. Overexpression of these genes demonstrated a direct impact on viral replication against wildtype CHIKV. These findings shed light on the mechanism of action of our vaccine and highlight the potential of targeting IFNγ-regulated antiviral genes for developing effective vaccines against CHIKV. Our results provided a foundation for investigating the broad-use application of IFN-γ against other alphaviruses for vaccine or therapeutic design. We evaluated the effects of increasing levels of exogenous hIFNγ on Mayaro virus (MAYV), Ross River virus (RRV), and Venezuelan Equine Encephalitis virus (VEEV). We observed a positive dose-dependent relationship between hIFNγ and decreasing viral titers for all three viruses. Interestingly, we also observed similar patterns of GBP upregulation with MAYV and RRV, both Old World alphaviruses, but not with VEEV, a New World alphavirus. This finding may indicate an alternative IFNγ-stimulated pathway responsible for controlling different alphaviruses. Overall, these studies establish a fundamental role of IFNγ in controlling viral infection and highlight its potential use in both vaccine and therapeutic intervention. While LAVs are a gold standard for developing immunity against a virus, the urgency of responding to an active and deadly pandemic has promoted the use of faster strategies such as mRNA vaccines. Once the viral sequence was known, these vaccines were comparatively quick to produce for SARS-CoV-2 and prevented millions of disease cases at the height of their introduction. However, the emergence of variants of concerns bypassing previous immunization efforts has demonstrated the need for complementary treatments such as antivirals to control disease. To that end, we evaluated several rhodium organometallic complexes as potential antivirals against SARS-CoV-2. We show that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(ICy)Cl2 and Cp*Rh(dpvm)Cl are non-toxic in Vero E6 and Calu3 cells and reduce SARS-CoV-2 plaque formation up to 99%. These complexes have previously demonstrated high antimicrobial activity against multiple antibiotic-resistance bacteria and with our results, support their potential application as pharmaceuticals, warranting further investigation into their activity. / Doctor of Philosophy / The global response to the COVID-19 pandemic, and its far-reaching impact, revealed significant shortcomings in public health preparedness for emerging viruses. Despite efforts to develop vaccines and antivirals to prevent and treat disease, current mitigation strategies have proven insufficient to eradicate the pathogen. The emergence of viral outbreaks caused by viruses such as chikungunya (CHIKV) and SARS-CoV-2 underscores the ongoing threat posed by emerging infectious diseases. Improved countermeasures are urgently needed to address gaps in vaccine and antiviral development. CHIKV is a mosquito-borne virus that has caused millions of infections across hundreds of countries with the emergent potential to become endemic in the US. Currently, there are no vaccines available to the public; therefore, it is important to generate and administer an effective vaccine before further spread of the virus. To this end, we developed innovative live-attenuated vaccines (LAVs) against CHIKV using a weakened chimeric backbone of CHIKV and its close relative, Semliki Forest virus (SFV), along with vaccine-driven expression of antiviral cytokines to control viral replication. Vaccination of highly susceptible mice with these cytokine-expressing vaccines produced significantly decreased side-effects compared to the parental virus not expressing the cytokines. Additionally, these viruses had significantly restricted viral replication capabilities while robustly protecting mice from a semi-lethal CHIKV infection. Our interferon-gamma (IFNγ) expressing vaccine had the greatest impact on viral replication, and we investigated the mechanism leading to this attenuation. To assess the clinical relevance of our vaccine platform, we redesigned the virus to express human IFNγ and identified a specific pattern of IFNγ-stimulated genes that are potentially responsible for limiting CHIKV replication. Furthermore, we demonstrated the broad therapeutic use of IFNγ against other medically relevant alphaviruses. Overall, these studies establish an improved mechanism to create safer vaccines without compromising efficacy and highlight the therapeutic potential of IFNγ against alphaviruses. Lastly, in a collaborative effort to respond to the COVID-19 pandemic, we also explored and characterized the use of a new class of antiviral drugs. With the advent of increasing drug resistance, it is essential to develop novel and resilient therapeutics. We demonstrated the first antiviral potential of rhodium organometallics, which was previously shown to be effective against multiple antibiotic-resistant bacteria. Two complexes demonstrated high virucidal activity against SARS-CoV-2 and low toxicity in mammalian cell lines. Moreover, these complexes can be further derivatized to improve efficacy, making them a promising new antiviral strategy.
318

Resolution of coronavirus disease 2019 (COVID-19)

Habas, Khaled S.A., Nganwuchu, Chinyere C., Shahzad, F., Gopalan, Rajendran C., Haque, M., Rahman, Sayeeda, Majumder, A.A., Nasim, Md. Talat 08 April 2020 (has links)
Yes / Introduction. Coronavirus disease 2019 (COVID-19) was first detected in China in December, 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. The effective option of antiviral therapy and vaccination are currently under evaluation and development. Areas covered. A literature search was performed using PubMed between December 1, 2019–June 23, 2020. This review highlights the current state of knowledge on the viral replication and pathogenicity, diagnostic and therapeutic strategies, and management of COVID-19. This review will be of interest to scientists and clinicians and make a significant contribution toward development of vaccines and targeted therapies to contain the pandemic. Expert Opinion. The exit strategy for a path back to normal life is required, which should involve a multi-prong effort toward development of new treatment and a successful vaccine to protect public health worldwide and prevent future COVID-19 outbreaks. Therefore, the bench to bedside translational research as well as reverse translational works focusing bedside to bench is very important and would provide the foundation for the development of targeted drugs and vaccines for COVID-19 infections. / Research carried out at TN laboratories are funded by the GrowMedtech, The Royal Society and University of Bradford. KH is supported by a project grant by the GrowMedtech awarded to TN. CW is funded by a Ph.D studentship.
319

Destruction catalytique à basses températures des composés organiques volatils (COV) / Total abatement of volatile organic compounds (VOC) by catalytic oxidation at low temperature

Ousmane, Mohamad 03 March 2010 (has links)
L’objectif de notre travail, était l’étude de deux classes de catalyseurs dans la réaction d’oxydation totale de COV. L’application visée étant la destruction à basse température de ces traces de polluants dans l’air. Des oxydes mixtes Co3O4-CeO2 ont été préparés par co-précipitation. Avec l’oxyde mixte (% atomique Co/Ce = 1), nous avons obtenu les meilleures performances catalytiques et montré que la réactivité étaient exaltée par une forte mobilité des oxygènes de coeur. Des catalyseurs à base d’or (2wt%) et de palladium (1wt%) ont été déposés sur des supports oxydes comme la cérine et le titane afin de favoriser une interaction métal support, ou sur un support alumine. Des solides à base d’alumine dopée au cérium, manganèse, fer et titane ont également été préparés. Pour l’or, l’évolution des performances catalytiques en fonction du support ont été les suivantes: Au2%/Al2O3 < Au2%/TiO2 < Au2%/CeO2, alors que pour le palladium nous avons obtenu les tendances suivantes : Pd1%/CeO2 < Pd1%/Al2O3 < Pd1%/TiO2. Pour l’Au, l’interaction métal support a permis d’expliquer les différences de réactivité alors que pour le palladium, l’activité est liée aux sites actifs de palladium Pd0/PdO présents à la surface. Avec les systèmes dopés, les résultats ont montré que les meilleurs catalyseurs étaient le Au2%/Ce5%/Al2O3 et le Pd1%/Ce5%/Al2O3. Cette exaltation a été attribuée à la grande mobilité des oxygènes en raison d’un défaut de structure induit par l’insertion des ions Al3+ au sein du réseau de la cérine et une forte interaction des particules très bien dispersées / The aim of the work was to study two classes of catalysts for the complete oxidation of volatile organic compounds. The target application for air pollution control is the total abatement of VOC at low temperature. Mixed oxide Co3O4-CeO2, were prepared by co-precipitation method. Among them, the mixed oxide corresponding to Co/Ce atomic ratio close to 1, was the best performing. The participation of surface oxygen species and high bulk mobile oxygen were the factors determining the high activity of Co30Ce in the total oxidation of propylene and toluene. Au (2wt%) and Pd (1wt%) catalysts were prepared over typical reducible oxides, such as CeO2 and TiO2. For comparison, catalysts over Al2O3, were also prepared. Moreover, the effect on the activity of Au and Pd supported over Al2O3 doped by cerium, manganese, iron and titanium was investigated. The so prepared Au and Pd catalysts were compared in the total oxidation of propylene. It was found that the activity of gold catalysts supported over un-doped oxides varied in the order: Au2%/Al2O3 < Au2%/TiO2 < Au2%/CeO2, while a different trend was observed for palladium catalysts: Pd1%/CeO2 < Pd1%/Al2O3 < Pd1%/TiO2. For Au catalysts, the nature of the support and the extent of interaction with the support are the key factors in determining the activity, whilst for the Pd supported ones, the activity seems to be governed by the nature of Pd species, Pd0/PdO, present in the catalyst. Au2%/Ce5%/Al2O3 and Pd1%/Ce5%/Al2O3 appear the best samples. The enhanced catalytic performances were attributed to high-oxygen mobility due to a defective ceria structure induced by the insertion of Al3+ ions into the lattice and also strong metal-support interaction between nanoparticles highly dispersed
320

Synthèse de matériaux nano structurés dans des solvants non aqueux / Synthesis of nanostructured materials in nonaqueous solvents

Raciulete, Monica 29 October 2010 (has links)
Dans la synthèse des matériaux catalytiques, deux aspects orientent en particulier les recherches actuelles: le contrôle de taille afin d’obtenir des nanoparticules finement divisées et le contrôle précis de la morphologie. Dans cette étude, nous avons utilisé les milieux non aqueux pour élaborer des matériaux catalytiques à base d’oxydes des métaux de transition (Ti, Zr, Mn). Trois méthodologies ont été employées pour la préparation des solides à base de TiO2. La synthèse dans les nitrates fondus dopés avec différents anions permet un boncontrôle des propriétés texturales des matériaux et de la nature des plans cristallins exposés. Les préparations utilisant le nitrate d’ammonium stabilisé avec des molécules organiques azotées conduit à des solides présentant des tailles et des formes de particules variables en fonction de la nature du stabilisateur. Le traitement à reflux dans des solvants organiques polaires conduit à l’obtention des supports TiO2 de grandes surfaces spécifiques. Pour la valorisation catalytique de ces matériaux, deux réactions appliquées au domaine de la photocatalyse ont été employées: la production d’H2 par déshydrogénation du méthanol etl’oxydation photocatalytique de l’acide formique. La réaction modèle de décomposition del’isopropanol a été utilisée comme test de caractérisation des propriétés acido-basiques de nossystèmes. La technique de nitrates fondus a été également appliqué avec succès pourl’obtention en une seule étape des catalyseurs supportés Mn-Zr et Mn-Ti. Ces catalyseursmontrent une excellente activité pour l’oxydation totale de composés organiques volatils(COV). / Two major challenges are particularly important for current research in the catalytic materials synthesis: preparation of finely divided particles and control of their shape. In this work we used non aqueous solvents to prepare catalytic materials containing transition metals oxides (Ti, Mn, Zr). Three techniques were applied to prepare TiO2-based solids. Reactions in molten alkali metal nitrates doped with different anions offered good control of textural properties and of the nature of exposed facets of nanocrystalline particles. Synthesis in molten ammonium nitrate stabilized with organic nitrogen-containing compounds provided TiO2 solids with variable size and shape as a function of stabilizer used. The reflux treatment in polar organic solvents leads to titania supports having high specific surface area. Two reactions from the field of photocatalysis were employed to valorize the obtained catalysts: H2 production by methanol dehydrogenation and photocatalytic oxidation of formic acid. Isopropanol decomposition has been used to determine the acid-base properties of the solids. Molten nitrate technique was then successfully applied in order to obtain in one-step highly dispersed Mn-Zr and Mn-Ti supported oxide catalysts. These systems showed excellent activity for the total oxidation of volatile organic compounds (VOC).

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