DOCSLIB.ORG

Elucidation of the Roles of PTN and ISG15 in RSV Cytopathogenesis: Possible Biomarkers of Severe Disease?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Elucidation of the Roles of PTN and ISG15 in RSV Cytopathogenesis: Possible Biomarkers of Severe Disease? DOCTOR OF PHILOSOPHY Elucidation of the roles of PTN and ISG15 in RSV cytopathogenesis: possible biomarkers of severe disease? Groves, Helen Award date: 2018 Awarding institution: Queen's University Belfast Link to publication Terms of use All those accessing thesis content in Queen’s University Belfast Research Portal are subject to the following terms and conditions of use • Copyright is subject to the Copyright, Designs and Patent Act 1988, or as modified by any successor legislation • Copyright and moral rights for thesis content are retained by the author and/or other copyright owners • A copy of a thesis may be downloaded for personal non-commercial research/study without the need for permission or charge • Distribution or reproduction of thesis content in any format is not permitted without the permission of the copyright holder • When citing this work, full bibliographic details should be supplied, including the author, title, awarding institution and date of thesis Take down policy A thesis can be removed from the Research Portal if there has been a breach of copyright, or a similarly robust reason. If you believe this document breaches copyright, or there is sufficient cause to take down, please contact us, citing details. Email: [email protected] Supplementary materials Where possible, we endeavour to provide supplementary materials to theses. This may include video, audio and other types of files. We endeavour to capture all content and upload as part of the Pure record for each thesis. Note, it may not be possible in all instances to convert analogue formats to usable digital formats for some supplementary materials. We exercise best efforts on our behalf and, in such instances, encourage the individual to consult the physical thesis for further information. Download date: 02. Oct. 2021 Elucidation of the roles of PTN and ISG15 in RSV cytopathogenesis: Possible biomarkers of severe disease? Helen Elizabeth Groves MB BCh BAO (Hon) School of Medicine, Dentistry and Biomedical Sciences, The Queen’s University of Belfast Thesis offered to The Queen’s University of Belfast for the degree of Doctor of Philosophy June 2018 Acknowledgements I would like to thank everyone who has supported and assisted me over the past few years in the preparation of this thesis work. I would particularly like to thank both of my supervisors, Dr Ultan Power and Prof. Mike Shields for their patience and encouragement throughout. I thank Dr Ultan Power for teaching me the scientific method, from the basics of how to pipette, the intricacies of scientific experimental design, through to critical thinking, problem solving and the drive for innovative science. I thank Prof. Shields for his encouragement, pragmatism and enthusiasm for the clinical application of scientific research. I commend him for his passion in teaching me the joy of robust statistical methodology and I hope one day to understand this as well as he does. I would like to thank Dr Lindsay Broadbent, Dr Hong Guo‐Parke, Dr Lyndsey Ferguson and Ms Andrena Millar for their training, guidance and friendship throughout my PhD work, as well as all of the other colleagues and students who supported me in their journey through the fourth floor of the Medical Biology Centre. I am grateful to all of the parents and the infants who took part in this research. Without them this work could not have been possible. I would also like to thank the staff of the Royal Jubilee Maternity Hospital, Belfast and the Royal Belfast Hospital for Sick Children for their assistance and support in recruiting infants. I thank the Wellcome Trust for their backing and financial support in completing this PhD. I am deeply grateful to my fiancé Andrew who has supported me unwaveringly during the business and challenges of this PhD work. I love him all the more for the faithfulness, kindness, patience and love he has shown me. 2 I thank my parents for their encouragement and unshakable backing throughout a lifetime of education, especially to my mother who taught me how to learn. Finally, I praise God, who enabled me to undertake this work and has given me innumerable blessings. For from Him and through Him and for Him are all things. 3 Statement of work contribution All work included in this thesis was conducted by myself (Dr Helen Groves). This included consenting and recruiting all participants, nasal sampling and processing of samples, as well as all laboratory work and data analysis detailed in this thesis. Acknowledgements of other contributions Prior to commencing this thesis work, an extensive microarray study was undertaken comparing pan‐genomic transcriptome responses in WD‐PNECs derived from cohorts of infants with histories of mild and severe RSV disease. This work was completed by Dr Hong Guo‐Parke who kindly contributed pleiotrophin microarray data. In addition, Dr Guillermo Lopez Campos performed analysis of the microarray data for pleiotrophin. This pleiotrophin data is presented in figure 25a. Dr Olivier Touzelet kindly contributed pleiotrophin ELISA data shown in figure 25b. qRT‐PCR analysis of cDNA from WD‐PNECs derived from cohorts of infants with histories of mild and severe RSV disease is presented in figure 39. I performed this work while being trained by Dr Lindsay Broadbent and she therefore contributed the data for analysis. Dr Lindsay Broadbent kindly contributed data for PTN pretreatment in WD‐PBECs shown in figure 31c. 4 Abstract Respiratory syncytial virus (RSV) infection is the most common cause of severe lower respiratory tract infection in infants under two years old. Sparking seasonal epidemics, RSV contributes to around 20,000 admissions to hospital in the UK annually and many require intensive care support. Peak incidences of severe RSV disease occur between 6 weeks and 6 months of age. Despite over 60 years of research since its discovery, no RSV vaccine or specific therapy exists. The only preventative strategy against RSV is the monoclonal antibody palivizumab, which is very expensive and, accordingly, only available to those infants at known high risk of severe RSV disease, including preterm infants and those with congenital heart conditions or bronchpulmonary dysplasia. As the majority of infants hospitalised with RSV have no known predisposing risk factor for severe illness, the benefits of palivizumab for managing the impact of RSV is very restricted. Considerable challenges in performing research in vulnerable young infants has slowed progress in RSV research. Animal models only partially reflect RSV‐human host interactions and thus extrapolation of results from these models to human responses is of limited value. Study of autopsy specimens from infants who succumbed to RSV infection identified that the infection is restricted primarily to the airway epithelium. As such, research aimed at detecting innate immune responses of human airway epithelium to RSV is likely to yield crucial insights into the cytopathogenesis of this infection. It has previously been demonstrated that an ex‐vivo/in‐vitro model of human airway epithelium/RSV interactions, termed well‐differentiated primary paediatric nasal epithelial cell cultures (WD‐PNECs), provides a reasonable surrogate for in vivo responses. Because of the strong association of severe RSV disease with prematurity and young age, the first part of this thesis describes the utilisation of the WD‐PNEC model to establish and 5 characterise unique nasal samples from preterm and term infants at birth and repeated at one‐year old. This work is the first description of morphologically and physiologically authentic WD‐PNEC cultures generated from term and preterm newborn infants and as such represents an exceptional opportunity to study RSV‐human host interactions in early life. We found that newborn term‐ and preterm‐derived WD‐PNECs were morphologically indistinguishable under light or fluorescent microscopy analysis. However, interestingly, newborn WD‐PNECs demonstrated significantly higher proportions of goblet cells compared to one‐year repeat WD‐PNECs. This finding indicates the possibility of increased mucous production in newborn infants, which may, in part, explain their susceptibility to more severe RSV disease. Importantly, we demonstrated nasal sampling to be a safe, minimally invasive method performed consistently with high rates of success. Furthermore, we were also able to successfully freeze, thaw, and subsequently differentiate the nasal epithelial cells. This confirmed the exciting possibility of storing newborn ‘‘naive’’ airway epithelial cells (AECs) indefinitely for use in subsequent experimentation, e.g., once clinical phenotypes, like severe RSV or asthma, have been established. We next sought to establish if differential RSV‐induced innate immune responses of airway epithelial cells could account, at least in part, for the increased susceptibility of preterm and very young infants to severe RSV disease. To investigate this, we infected (or mock‐infected) WD‐PNEC cultures established from term and preterm infants at birth and repeated at one‐ year‐old. No significant differences in cytopathology or viral growth kinetics were evident in WD‐PNECs derived from any cohort following RSV infection. However, crucially, we observed significantly higher secretion of interferon 1 (IL‐29) (P<0.01), IP‐10 (CXCL‐10) (P<0.05) and RANTES (CCL‐5) (P<0.05) following RSV infection of one‐year‐derived WD‐PNEC cultures compared to newborn‐derived cultures. These novel findings suggest airway 6 epithelium innate immune responses
Load more

Recommended publications
  • Optumrx Brand Pipeline Forecast
    RxOutlook® 1st Quarter 2019 OptumRx brand pipeline forecast Route of Regulatory Estimated Specialty Orphan Drug name Generic name Company Drug class Therapeutic use administration status release date drug drug 2019 Possible launch date Ophthalmological DS-300 DS-300 Eton undisclosed SC Filed NDA 2019 unknown N disease anti-sclerostin Evenity romosozumab Amgen Osteoporosis SC Filed NDA 2/2019 Y N monoclonal antibody tetrahydrofolate iclaprim iclaprim Motif Bio Bacterial infections IV Filed NDA 2/13/2019 Y Y dehydrogenase inhibitor tazarotene/ IDP-118 Valeant retinoid/ corticosteroid Psoriasis TOP Filed NDA 2/15/2019 N N halobetasol adenosine deaminase Mavenclad cladribine Merck/ Teva resistant Multiple sclerosis PO Filed NDA 2/15/2019 Y N deoxyadenosine analog Lotemax Gel loteprednol Valeant corticosteroid Ocular inflammation OP Filed NDA 2/25/2019 N N Nex Gen etabonate turoctocog alfa glyco-PEGylated factor NN-7088 Novo Nordisk Hemophilia IV/SC Filed BLA 2/27/2019 Y N pegol VIII derivative selective sphingosine-1 BAF-312 siponimod Novartis phosphate receptor Multiple sclerosis PO Filed NDA 3/1/2019 Y N agonist midazolam midazolam UCB benzodiazepine Seizures Intranasal Filed NDA 3/1/2019 N Y (USL-261) XeriSol glucagon Xeris glucagon analog Diabetes mellitus SC Filed NDA 3/1/2019 N N Glucagon optum.com/optumrx 1 RxOutlook® 1st Quarter 2019 Route of Regulatory Estimated Specialty Orphan Drug name Generic name Company Drug class Therapeutic use administration status release date drug drug dopamine receptor JZP-507 sodium oxybate Jazz Narcolepsy
    [Show full text]
  • Microorganisms-07-00521-V2.Pdf
    microorganisms Review Are Community Acquired Respiratory Viral Infections an Underestimated Burden in Hematology Patients? Cristian-Marian Popescu 1,* , Aurora Livia Ursache 2, Gavriela Feketea 1 , Corina Bocsan 3, Laura Jimbu 1, Oana Mesaros 1, Michael Edwards 4,5, Hongwei Wang 6, Iulia Berceanu 7, Alexandra Neaga 1 and Mihnea Zdrenghea 1,7,* 1 Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes str., 400012 Cluj-Napoca, Romania; [email protected] (G.F.); [email protected] (L.J.); [email protected] (O.M.); [email protected] (A.N.) 2 The Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăs, tur 3-5, 400372 Cluj-Napoca, Romania; [email protected] 3 Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Ha¸tieganuUniversity of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; [email protected] 4 National Heart and Lung Institute, St Mary’s Campus, Imperial College London, London W2 1PG, UK; [email protected] 5 Medical Research Council (MRC) and Asthma UK Centre in Allergic Mechanisms of Asthma, London W2 1PG, UK 6 School of Medicine, Nanjing University, 22 Hankou Road, Nanjing 210093, China; [email protected] 7 Department of Hematology, Ion Chiricuta Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania; [email protected] * Correspondence: [email protected] (C.-M.P.); [email protected] (M.Z.) Received: 8 October 2019; Accepted: 31 October 2019; Published: 2 November 2019 Abstract: Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine.
    [Show full text]
  • Repurposing Nucleoside Analogs for Human Coronaviruses
    ANTIVIRAL AGENTS crossm Repurposing Nucleoside Analogs for Human Coronaviruses Keivan Zandi,a,b Franck Amblard,a,b Katie Musall,a,b Jessica Downs-Bowen,a,b Ruby Kleinbard,a,b Adrian Oo,a,b Dongdong Cao,c Bo Liang,c Olivia O. Russell,a,b Tamara McBrayer,a,b Leda Bassit,a,b Baek Kim,a,b Raymond F. Schinazia,b aCenter for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Downloaded from bChildren’s Healthcare of Atlanta, Atlanta, Georgia, USA cDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA ABSTRACT Coronavirus disease 2019 (COVID-19) is a serious illness caused by se- vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or CoV-2). Some reports claimed certain nucleoside analogs to be active against CoV-2 and thus needed con- firmation. Here, we evaluated a panel of compounds and identified novel nucleoside analogs with antiviral activity against CoV-2 and HCoV-OC43 while ruling out others. http://aac.asm.org/ Of significance, sofosbuvir demonstrated no antiviral effect against CoV-2, and its triphosphate did not inhibit CoV-2 RNA polymerase. KEYWORDS SARS-CoV-2, HCoV-OC43, antiviral agents, nucleoside analogs, remdesivir, sofosbuvir, emtricitabine, lamivudine, COVID-19, Coronaviridae oronavirus disease 2019 (COVID-19) has emerged as a global pandemic with Csignificant morbidity and mortality caused by the severe acute respiratory syn- on December 16, 2020 by guest drome coronavirus 2 (SARS-CoV-2 or CoV-2). CoV-2-infected individuals usually develop mild to severe flulike symptoms, whereas other individuals (particularly the elderly harboring underlying chronic health complications, such as diabetes and heart disease, or immunocompromised individuals) are particularly prone to develop severe to fatal clinical outcomes (1, 2).
    [Show full text]
  • Respiratory Syncytial Virus
    RSV Respiratory syncytial virus RSV (Respiratory syncytial virus) is a leading cause of acute respiratory infections. RSV can exploit host immunity and cause a strong inflammatory response that leads to lung damage and virus dissemination. There is a single RSV serotype with two major antigenic subgroups, A and B. RSV is a non-segmented negative-sense single-stranded enveloped RNA virus that belongs to the family of Paramyxoviridae, genus Pneumovirus, subfamily Pneumovirinae. Its 10 genes encode 11 proteins since two overlapping open reading frames in the M2 mRNA yield two distinct matrix proteins, M2-1 and M2-2. The viral envelope contains three proteins, the G glycoprotein, the fusion (F) glycoprotein, and the small hydrophobic (SH) protein. The RSV virus comprises five other structural proteins, the large (L) protein, nucleocapsid (N), phosphoprotein (P), matrix (M), and M2-1, and two non-structural proteins (NS1 and NS2). www.MedChemExpress.com 1 RSV Inhibitors Ac-CoA Synthase Inhibitor1 ALS-8112 Cat. No.: HY-104032 Cat. No.: HY-12983 Ac-CoA Synthase Inhibitor1 is a potent, reversible ALS-8112 is a potent and selective respiratory acetate-dependent acetyl-CoA synthetase 2 syncytial virus (RSV) polymerase inhibitor. The (ACSS2) inhibitor with an IC50 of 0.6 µM. Ac-CoA 5'-triphosphate form of ALS-8112 inhibits RSV Synthase Inhibitor1 inhibits the respiratory polymerase with an IC50 of 0.02 μM. syncytial virus (RSV). Purity: 99.23% Purity: 99.97% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg Size: 10 mM × 1 mL, 1 mg, 5 mg, 10 mg, 50 mg, 100 mg Amentoflavone ent-11β-Hydroxyatis-16-ene-3,14-dione (Didemethyl-ginkgetin) Cat.
    [Show full text]
  • Study Initiation Q4 2017 - 18
    Study Initiation Q4 2017 - 18 Reasons for Research Ethics Integrated Research Date Site Non- Date of First Date Site . Date Site HRA Approval Date Site Date Site Ready Benchmark delay Committee Application System Name of Trial Confirmed By Confirmation Patient Reasons for Delay Comments Invited Selected Date Confirmed To Start Met correspond Reference Number Number Sponsor Status Recruited to: HRA pack was received prematurely PLATO - PersonaLising Anal cancer radioTherapy dOse - 16/YH/0157 204585 21/07/2016 12/04/2017 20/07/2016 30/06/2017 13/06/2017 Please Select... 14/08/2017 21/06/2017 Yes A - Permissions delayed/denied from sponsor. Delays with site capacity Both Incorporating Anal Cancer Trials (ACT) ACT3, ACT4 and ACT5 and capability review. MAnagement of high bleeding risk patients post bioresorbable A - Site documentation delays. Rare 17/LO/0108 221119 polymer coated STEnt implantation with an abbReviated versus 23/12/2016 10/04/2017 10/04/2017 29/03/2017 04/04/2017 Please Select... 30/05/2017 01/08/2017 No A - Permissions delayed/denied NHS Provider patient group prolonged DAPT regimen – MASTER DAPT Delays by sponsor - portfolio adoption awaited and then site pharmacy concerns remained unresolved by Cereal Bar or oral supplementation with tablets to increase serum Site declined to Site Not 16/LO/1130 187152 01/02/2017 05/05/2017 01/11/2016 D - Sponsor Delays sponsor and it was decided to close Sponsor folate in young pregnant women participate Confirmed BSUH as a site on the 17/08/17, therefore we did not open as a site for this study 70 Day target date missed due to sponsor delays with devices and delays with MHRA & HRA Approvals.
    [Show full text]
  • A Meeting Report from the 6Th Isirv Antiviral Group Conference T
    Antiviral Research 167 (2019) 45–67 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference T ∗ John H. Beigela, , Hannah H. Namb, Peter L. Adamsc, Amy Kraffta, William L. Inced, Samer S. El-Kamaryd, Amy C. Simse a National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA bNorthwestern University, Feinberg School of Medicine, Chicago, IL, USA c Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), Washington, DC, USA d Division of Antiviral Products, Office of Antimicrobial Products, Office of New Drugs, Center for Drug Evaluation and Research, U.S Food and Drug Administration, Silver Spring, MD, USA e Gillings School of Global Public Health, Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA ARTICLE INFO ABSTRACT Keywords: The International Society for Influenza and other Respiratory Virus Diseases held its 6th Antiviral Group (isirv- Influenza AVG) conference in Rockville, Maryland, November 13–15, 2018. The three-day program was focused on Respiratory syncytial virus therapeutics towards seasonal and pandemic influenza, respiratory syncytial virus, coronaviruses including Coronavirus MERS-CoV and SARS-CoV, human rhinovirus, and other respiratory viruses. Updates were presented on several Antiviral therapy influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, Host-directed therapeutics pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies in- cluding nitazoxanide, eritoran, and diltiazem.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Review : Imunoterapi Penanganan Infeksi Virus
    Jurnal Mandala Pharmacon Indonesia, Vol 7.No.1 Juni 2021 Avaiable online at www.jurnal-pharmaconmw.com/jmpi p-ISSN : 2442-6032 e-ISSN : 2598-9979 Review : Imunoterapi Penanganan Infeksi Virus Usmar1, Andi Maqhfirah Nurul Fitri1, Dewi Yuliana2, Firzan Nainu1* 1Fakultas Farmasi, Universitas Hasanuddin, Makassar 2Fakultas Farmasi, Universitas Muslim Indonesia, Makassar ABSTRAK Penyakit menular akibat virus merupakan salah satu perkembangan yang pesat terutama dalam kondisi masalah kesehatan global yang mempengaruhi sistem pandemi COVID-19 yang dihadapi saat ini. Meskipun kesehatan masyarakat dan ekonomi di seluruh dunia. terapi dan obat-obatan yang digunakan dalam bidang Hal tersebut mendorong disusunnya artikel ini untuk imunofarmakologi masih terbatas serta banyak hal yang mendiskusikan relevansi dan pentingnya imunoterapi belum dapat ditemukan, namun teknologi baru dan dalam menentukan pilihan terapetik terkait infeksi kemajuan pesat dalam pengetahuan tentang regulasi virus, dengan menitikberatkan pembahasan pada sistem imun telah menjadikan imunoterapi sebagai ketersediaan pilihan vaksin dan obat yang telah bidang yang memiliki potensi besar dan menjanjikan ditemukan untuk membantu manusia melawan berbagai dalam penanganan infeksi virus maupun patogen lain. jenis infeksi yang disebabkan oleh virus. Penulisan Oleh karena itu, konsep imunoterapi serta relevansinya artikel review naratif ini dilakukan menggunakan dengan penyakit manusia merupakan salah satu solusi metode analisis pustaka primer maupun sekunder yang menawarkan pilihan baru
    [Show full text]
  • International Nonproprietary Names for Pharmaceutical Substances (INN)
    WHO Drug Information, Vol. 31, No. 1, 2017 Recommended INN: List 77 International Nonproprietary Names for Pharmaceutical Substances (INN) RECOMMENDED International Nonproprietary Names: List 77 Notice is hereby given that, in accordance with paragraph 7 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances [Off. Rec. Wld Health Org., 1955, 60, 3 (Resolution EB15.R7); 1969, 173, 10 (Resolution EB43.R9); Resolution EB115.R4 (EB115/2005/REC/1)], the following names are selected as Recommended International Nonproprietary Names. The inclusion of a name in the lists of Recommended International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–113) and Recommended (1–74) International Nonproprietary Names can be found in Cumulative List No. 16, 2015 (available in CD-ROM only). Dénominations communes internationales des Substances pharmaceutiques (DCI) Dénominations communes internationales RECOMMANDÉES: Liste 77 Il est notifié que, conformément aux dispositions du paragraphe 7 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques [Actes off. Org. mond. Santé, 1955, 60, 3 (résolution EB15.R7); 1969, 173, 10 (résolution EB43.R9); résolution EB115.R4 (EB115/2005/REC/1)] les dénominations ci-dessous sont choisies par l’Organisation mondiale de la Santé en tant que dénominations communes internationales recommandées. L’inclusion d’une dénomination dans les listes de DCI recommandées n’implique aucune recommandation en vue de l’utilisation de la substance correspondante en médecine ou en pharmacie. On trouvera d’autres listes de Dénominations communes internationales proposées (1–113) et recommandées (1–74) dans la Liste récapitulative No.
    [Show full text]
  • Repurposing of FDA Approved Drugs
    Antiviral Drugs (In Phase IV) ABACAVIR GEMCITABINE ABACAVIR SULFATE GEMCITABINE HYDROCHLORIDE ACYCLOVIR GLECAPREVIR ACYCLOVIR SODIUM GRAZOPREVIR ADEFOVIR DIPIVOXIL IDOXURIDINE AMANTADINE IMIQUIMOD AMANTADINE HYDROCHLORIDE INDINAVIR AMPRENAVIR INDINAVIR SULFATE ATAZANAVIR LAMIVUDINE ATAZANAVIR SULFATE LEDIPASVIR BALOXAVIR MARBOXIL LETERMOVIR BICTEGRAVIR LOPINAVIR BICTEGRAVIR SODIUM MARAVIROC BOCEPREVIR MEMANTINE CAPECITABINE MEMANTINE HYDROCHLORIDE CARBARIL NELFINAVIR CIDOFOVIR NELFINAVIR MESYLATE CYTARABINE NEVIRAPINE DACLATASVIR OMBITASVIR DACLATASVIR DIHYDROCHLORIDE OSELTAMIVIR DARUNAVIR OSELTAMIVIR PHOSPHATE DARUNAVIR ETHANOLATE PARITAPREVIR DASABUVIR PENCICLOVIR DASABUVIR SODIUM PERAMIVIR DECITABINE PERAMIVIR DELAVIRDINE PIBRENTASVIR DELAVIRDINE MESYLATE PODOFILOX DIDANOSINE RALTEGRAVIR DOCOSANOL RALTEGRAVIR POTASSIUM DOLUTEGRAVIR RIBAVIRIN DOLUTEGRAVIR SODIUM RILPIVIRINE DORAVIRINE RILPIVIRINE HYDROCHLORIDE EFAVIRENZ RIMANTADINE ELBASVIR RIMANTADINE HYDROCHLORIDE ELVITEGRAVIR RITONAVIR EMTRICITABINE SAQUINAVIR ENTECAVIR SAQUINAVIR MESYLATE ETRAVIRINE SIMEPREVIR FAMCICLOVIR SIMEPREVIR SODIUM FLOXURIDINE SOFOSBUVIR FOSAMPRENAVIR SORIVUDINE FOSAMPRENAVIR CALCIUM STAVUDINE FOSCARNET TECOVIRIMAT FOSCARNET SODIUM TELBIVUDINE GANCICLOVIR TENOFOVIR ALAFENAMIDE GANCICLOVIR SODIUM TENOFOVIR ALAFENAMIDE FUMARATE TIPRANAVIR VELPATASVIR TRIFLURIDINE VIDARABINE VALACYCLOVIR VOXILAPREVIR VALACYCLOVIR HYDROCHLORIDE ZALCITABINE VALGANCICLOVIR ZANAMIVIR VALGANCICLOVIR HYDROCHLORIDE ZIDOVUDINE Antiviral Drugs (In Phase III) ADEFOVIR LANINAMIVIR OCTANOATE
    [Show full text]
  • Update on Current Views and Advances on RSV Infection (Review)
    INTERNATIONAL JOURNAL OF MOleCular meDICine 46: 509-520, 2020 Update on current views and advances on RSV infection (Review) IOANNIS N. MAMMAS1-3, SIMON B. DRYSDALE4,5, BARBARA RATH6-8, MARIA THEODORIDOU2, GEORGIA PAPAIOANNOU9, ALEXIA PAPATHEODOROPOULOU10, EIRINI KOUTSOUNAKI11,12, CHRYSSIE KOUTSAFTIKI13, ELEFTHERIA KOZANIDOU14, VASSILIS ACHTSIDIS15, PARASKEVI KOROVESSI16, GEORGE P. CHROUSOS2 and DEMETRIOS A. SPANDIDOS1 1Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion; 2First Department of Paediatrics, University of Athens School of Medicine, 11527 Athens; 3Paediatric Clinic, 34500 Aliveri, Greece; 4St. George's, University of London, London SW17 0RE; 5Department of Paediatric Infectious Diseases, St. George's University Hospitals NHS Foundation Trust, London SW17 0QT, UK; 6Vienna Vaccine Safety Initiative, D‑10437 Berlin, Germany; 7Université Bourgogne Franche‑Comté, 25000 Besancon, France; 8University of Nottingham School of Medicine, Nottingham NG7 2UH, UK; 9Department of Paediatric Radiology, ‘Mitera’ Children's Hospital, 15123 Athens; 10Paediatric Intensive Care Unit (PICU), ‘Aglaia Kyriakou’ Children's Hospital, 11527 Athens; 11Neonatal Department, ‘Alexandra’ Maternity Hospital, 15123 Athens; 12Neonatal Department, ‘Helena Venizelou’ Maternity Hospital, 11521 Athens; 13Paediatric Intensive Care Unit (PICU), ‘Penteli’ Children's Hospital, 15236 Penteli; 142nd Department of Internal Medicine, ‘St Panteleimon’ General Hospital of Nikaia, 18454 Piraeus, Greece; 15Department of Ophthalmology, Royal Cornwall Hospitals, Cornwall TR1 3LQ, UK; 16Department of Paediatrics, ‘Penteli’ Children's Hospital, 15236 Penteli, Greece Received May 15, 2020; Accepted June 15, 2020 DOI: 10.3892/ijmm.2020.4641 Abstract. Respiratory syncytial virus (RSV) infection repre- on recent advances in the epidemiology, pathogenesis, diag- sents an excellent paradigm of precision medicine in modern nosis, prognosis, clinical management and prevention of RSV paediatrics and several clinical trials are currently performed infection in childhood.
    [Show full text]
  • Lionel Dylan Jensen
    Inhibition and Enhancement of Respiratory Syncytial Virus Replication by Nucleoside Analogues and Bis(indole) Compounds by Lionel Dylan Jensen A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Virology Department of Medical Microbiology and Immunology University of Alberta © Lionel Dylan Jensen, 2018 Abstract Respiratory syncytial virus (RSV) is an Orthopneumovirus that infects the epithelium of the airways. Severe RSV infection of the lower respiratory tract in infants is a leading cause of pediatric hospitalizations. RSV also causes substantial morbidity in immunocompromised and elderly populations. Palivizumab, a humanized monoclonal antibody, is available for the prophylactic treatment of high-risk infants. However, this intervention is expensive and has a limited impact on annual hospitalization rates caused by RSV. No vaccine is available to prevent RSV infection and no efficacious antivirals are available to treat active infection. To address the burden of disease imposed by RSV, this project sought to develop and implement a screening assay to identify compounds with antiviral activity against RSV. Different screening protocols were examined as platforms for testing antiviral activity. The first protocol quantified changes to RSV replication complex morphology during antiviral treatment. Through confocal microscopy, changes to replication complex morphology were identified as early as six hours post infection. However, this assay was hindered by the low signal intensity produced by replication complexes. Therefore, alternative RSV-antiviral screening protocols were investigated. Subsequent protocols quantified initial monolayer infection, or quantified RSV progeny production, via colourimetric or immunofluorescence (IF) staining. Automated detection of IF-stained RSV-infected cells was conducted using a high content imaging system.
    [Show full text]