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      Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

      Author(s): 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 ,   1 , 1 , 1 , 1 , 1 , 1 , 1 , 1
      Publication date (Electronic):
      Journal: The New England journal of medicine
      Publisher: Massachusetts Medical Society

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          Abstract

          World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).

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          Most cited references5

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          Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials

          Adrian Harris (2005)
          The Lancet, 365(9472), 1687-1717
          Article 0 comments Cited 616 times – based on 0 reviews     Review now
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            The type I interferon signaling pathway is a target for glucocorticoid inhibition.

            Jana Dobrovolna, Lionel B Ivashkiv, Inez Rogatsky … (2010)
            Type I interferon (IFN) is essential for host defenses against viruses; however, dysregulated IFN signaling is causally linked to autoimmunity, particularly systemic lupus erythematosus. Autoimmune disease treatments rely on glucocorticoids (GCs), which act via the GC receptor (GR) to repress proinflammatory cytokine gene transcription. Conversely, cytokine signaling through cognate Jak/STAT pathways is reportedly unaffected or even stimulated by GR. Unexpectedly, we found that GR dramatically inhibited IFN-stimulated gene (ISG) expression in macrophages. The target of inhibition, the heterotrimeric STAT1-STAT2-IRF9 (ISGF3) transcription complex, utilized the GR cofactor GRIP1/TIF2 as a coactivator. Consequently, GRIP1 knockdown, genetic ablation, or depletion by GC-activated GR attenuated ISGF3 promoter occupancy, preinitiation complex assembly, and ISG expression. Furthermore, this regulatory loop was restricted to cell types such as macrophages expressing the GRIP1 protein at extremely low levels, and pharmacological disruption of the GR-GRIP1 interaction or transient introduction of GRIP1 restored RNA polymerase recruitment to target ISGs and the subsequent IFN response. Thus, type I IFN is a cytokine uniquely controlled by GR at the levels of not only production but also signaling through antagonism with the ISGF3 effector function, revealing a novel facet of the immunosuppressive properties of GCs.
            Article 0 comments Cited 67 times – based on 0 reviews     Review now
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              Pharmacokinetics and pharmacodynamics of IFN-beta 1a in healthy volunteers.

              A Buchwalder, I Trinchard-Lugan, I Trinchard … (2000)
              The pharmacokinetics of recombinant human interferon-beta1a (IFN-beta1a) (Rebif, Ares-Serono, Geneva, Switzerland) were investigated in healthy volunteers following intravenous (i.v.) administration of increasing single doses of the drug (22 microg/6 million international units [MIU], 44 microg/12 MIU, and 66 microg/18 MIU); i.v., intramuscular (i.m.), and subcutaneous (s.c.) administration of a 66-microg dose; and repeated s.c. administration of four 66-microg doses at 48-h intervals. The disposition of IFN-beta1a followed triexponential decay after i.v. administration (half-lives 3 min, 42 min, and 22 h, respectively). After s.c. and i. m. administration, absorption was the rate-limiting factor in the terminal phase. The median absolute bioavailabilities were 30% and 27%, respectively. The accumulation ratio after repeated s.c. injections was 2.4, and a terminal half-life of 66 h was observed. Intracellular 2-5A synthetase activity and serum neopterin and beta2-microglobulin concentrations increased after all IFN-beta1a injections and remained elevated following every-other-day administration. The local tolerance was good, and the systemic tolerance was satisfactory.
              Article 0 comments Cited 21 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (iso-abbrev): N Engl J Med
                Title: The New England journal of medicine
                Publisher: Massachusetts Medical Society
                ISSN (Electronic): 1533-4406
                ISSN (Print): 0028-4793
                Publication date (Electronic): February 11 2021
                Volume: 384
                Issue: 6
                Affiliations
                [1 ] The affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R.P.), and the University of Bristol, Bristol (E.A., S.B., H.B.C.C.-P., D.H., J.K., C.A.R., J.A.C.S.) - both in the United Kingdom; the World Health Organization, Geneva (A.-M.H.-R., M.-P.P., V.S., P. Lydon, M.C.M.-M., K.S., S.S.), the University of Bern, Bern (S.A., M.B., S. McGinty, S.T.), and Lausanne University Hospital, Lausanne (O.M.) - all in Switzerland; the Centre for the AIDS Programme of Research in South Africa, Durban (Q.A.K.), and the University of the Witwatersrand (J.N.) and the Wits Reproductive Health and HIV Institute (H.R.), Johannesburg - all in South Africa; the Institute of National Epidemiology, National Institutes of Health, University of the Philippines, Manila (M.M.A.); the Agency of Medicine and Medical Devices (C.H.G.) and Hospital Clínico San Carlos, Universidad Complutense de Madrid, Spanish Clinical Research Network, Instituto de Investigación Sanitaria San Carlos (A.P.), Madrid; INSERM, Paris (M.-P.K.), and Hospices Civils de Lyon, Lyon (F.A.) - both in France; the Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran (R.M.); the University of British Columbia, Vancouver (S. Murthy), and the Public Health Agency of Canada, Ottawa (M.I.S.) - both in Canada; the Public Health Foundation of India, New Delhi (K.S.R.), and the Indian Council of Medical Research, National AIDS Research Institute, Pune (S.G.) - both in India; the National Academy of Sciences of Buenos Aires (M.R.P.) and Fundación del Centro de Estudios Infectológicos (G.L.), Buenos Aires; Rafic Hariri University Hospital (P.A.H.) and the Ministry of Public Health (R.H.), Beirut, Lebanon; the Ministry of Health (A.M.A.-B.) and Infectious Diseases Hospital (A. Alhasawi), Kuwait City, Kuwait; Universidad Nacional de Colombia and Clinica Colsanitas (C.A.A.-M.) and the Ministry of Health (M.L.M.R.), Bogota, Colombia; the Ministry for Preventive Health, Riyadh, Saudi Arabia (A. Asiri, A. Alotaibi); Oslo University Hospital (P.A., A.B.-D.) and Research Council of Norway (J.-A.R.), Oslo; Secretaria de Salud de Honduras (N. Cerrato) and the National Autonomous University of Honduras (M.T.M.), Tegucigalpa; Penang Hospital, Penang (T.S.C.), and Hospital Sungai Buloh and Jalan Hospital, Selangor (S.K.) - both in Malaysia; University Hospital Center Mother Theresa (N. Como) and the National Agency for Medicines and Medical Devices (N.S.), Tirana, Albania; the HRB Clinical Research Facility, University College Cork, Cork (J.E.), and the Department of Health and Children, Dublin (P. Lennon, T.M.) - both in Ireland; Universidad Peruana Cayetano Heredia, Lima, Peru (P.J.G., E.G.); Vilnius University Hospital Santaros Klinikos (L.G.) and Vilnius University, Institute of Clinical Medicine (L.J.), Vilnius, Lithuania; Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M. Hassan, A.R.); the National Hepatology and Tropical Medicine Research Institute (M. Hassany) and the Ministry of Health and Population (H.Z.), Cairo; the National Institute of Health Research and Development (I.I.) and Rumah Sakit Umum Pusat Persahabatan (M.R.R.), Jakarta, Indonesia; the Italian Medicines Agency, Rome (N.M.), and the University of Verona, Verona (E.T.) - both in Italy; the Ministry of Health (S. Manevska) and the University Clinic of Infectious Diseases and Febrile Conditions (M.S.), Skopje, North Macedonia; the Oswaldo Cruz Foundation, Rio de Janeiro (E.P.N., P.P.S.R.); and the Finnish Institute for Health and Welfare and the University of Finland (M.P.) and Helsinki University Hospital (K.A.O.T.), Helsinki, and South Karelian Central Hospital, Lappeenranta (K.A.O.T.) - all in Finland.
                Article
                DOI: 10.1056/NEJMoa2023184
                PMC ID: 7727327
                PubMed ID: 33264556
                SO-VID: d318d070-f045-49d7-b44a-94f2cc44873b
                Copyright © Copyright © 2020 Massachusetts Medical Society.
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