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DOI: 10.1055/s-2006-944278
Pharmakotherapie bei Schwerem Akutem Respiratorischem Syndrom (SARS)
Pharmacotherapy of Severe Acute Respiratory Syndrome (SARS)Publikationsverlauf
eingereicht 10. 7. 2006
akzeptiert 26. 7. 2006
Publikationsdatum:
16. November 2006 (online)
![](https://www.thieme-connect.de/media/pneumologie/200611/lookinside/thumbnails/10.1055-s-2006-944278-1.jpg)
Zusammenfassung
Das schwere akute respiratorische Syndrom (SARS) ist die erste bedeutende neue Infektionskrankheit dieses Jahrtausends und wird durch das SARS-Coronavirus (SARS-CoV) hervorgerufen. SARS geht mit einer erheblichen Morbidität und Mortalität einher und trat erstmals als Epidemie von 2002 - 2003 auf. Bis heute ist noch kein spezifisch wirksames Therapeutikum gegen das SARS-Coronavirus gefunden worden. Aufgrund des schnellen Voranschreitens der Epidemie 2002 - 2003 war es nicht möglich, multizentrierte, kontrollierte, randomisierte Studien durchzuführen. Daher existieren noch keine allgemeingültigen therapeutischen Richtlinien für diese neue Viruserkrankung. Seit dem Ausbruch von SARS untersuchen Wissenschaftler potenziell wirksame Substanzen gegen das Virus hauptsächlich mittels In-vitro-Tests und an Tiermodellen. Die vorliegende Arbeit analysiert die derzeit zur Pharmakotherapie vorhandenen In-vitro- und In-vivo-Ergebnisse.
Abstract
Severe acute respiratory syndrome (SARS) constitutes the first new infectious disease of the current millennium. It is caused by the novel SARS-Coronavirus (SARS-CoV). SARS is related to a high morbidity and mortality and first appeared during an epidemic in 2002 - 2003. To date no specific therapy against the SARS-CoV is available. Due to the rapid spread of SARS during the epidemics in 2002 - 2003, randomised and controlled multicentre studies were not performed. Therefore, general guidelines have not been developed. Since the outbreak, scientists have been testing potential antiviral substances using in vitro and animal models. This study analyses the presently available in vitro and in vivo data on the pharmacotherapy of SARS.
Literatur
- 1 Groneberg D A, Poutanen S M, Low D E. et al . Treatment and vaccines for severe acute respiratory syndrome (SARS). Lancet Infect Dis. 2005; 5 147-155
- 2 Poon L L, Guan Y, Nicholls Y M. et al . The aetiology, origins and diagnosis of severe acute respiratory syndrome. Lancet Infect dis. 2004; 4 663-671
- 3 Reilley B, Herp M van, Sermand D. et al . SARS and Carlo Urbani. N Engl J Med. 2003; 348 1951-1952
- 4 World Health Organization (WHO) .Summary of propable SARS cases with onset of illness from 1. November 2002 to 31. July 2003. http//www.who.int/csr/sars/country/table2004_04_21/en 2003 (accessed feb 3, 2005)
- 5 World Health Organization Multicentre Collaborative Network for Severe Acute Respiratory Syndrome Diagnosis . A multicentre collaboration to investigate the cause of severe acute respiratory syndrome. Lancet. 2003; 361 1730-1733
- 6 Peiris J S, Lai S T, Poon L L. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003; 361 1319-1325
- 7 Drosten C, Gunter S, Preiser W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003; 348 1967-1976
- 8 Ksiazek T G, Erdmann D, Goldsmith C S. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003; 348 1953-1966
- 9 Zhang Q F, Cui J M, Huang X J. Morpholigy and morphogenesis of severe acute respiratory syndrome (SARS)-associated virus. Chin J Biochem Biophys. 2003; 35 587-591
- 10 Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol. 1997; 142 629-633
- 11 Sidell S, Wege H, ter Meulen V. The structure and replication of coronaviruses. Curr Top Microbiol Immunol. 1982; 99 131-163
- 12 Wege H, Sidell S, ter Meulen V. The biology and pathogenesis of Coronaviruses. Curr Top Microbiol Immunol. 1982; 99 165-200
- 13 Guan Y, Zheng B J, He Y Q. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science. 2003; 302 276-278
- 14 Bonn D. Wild animals could be source of SARS. Lancet Infect Dis. 2003; 3 395
- 15 Chan P KS, Tang J W. SARS: clinical presentation, transmission, pathogenesis and treatment options. Clinical Science. 2006; 110 193-204
- 16 Dietel M, Suttorp N, Zeitz M. Harrisons Innere Medizin, 16. Aufl. ABW-Wissenschaftsverlag 2005
- 17 Marra M A, Jones S J, Astell C R. The genome sequence of the SARS-associated coronavirus. Science. 2003; 300 1399-1404
- 18 Groneberg D A, Hilgenfeld R, Zabel P. Molecular mechanisms of severe acute respiratory syndrome (SARS). Respir Res. 2005; 6 8
- 19 Lai M M, Cavanagh D. The molecular biology of coronaviruses. Adv Virus Res. 1997; 48 1-100
- 20 Wentworth D E, Gillim-Ross L, Espina N. et al . Mice susceptible to SARS coronavirus. Emerge Infect Dis. 2004; 10 1293-1296
- 21 Martina B E, Haagmans B L, Kuikan T. Virology: SARS virus infection of cats and ferrets. Nature. 2003; 425 915
- 22 Tsui P T, Kwok M L, Yuen H. et al . Sevre acute respiratory syndrome: clinical outcome and prognostic correlates. Emerg Infect Dis. 2003; 9 1064-1069
- 23 Donnelly C A, Ghani A C, Leung G M. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003; 361 1761-1766
- 24 Bitnun A, Allen U, Heurter H. Children hospitalized with severe acute respiratory syndrome - related illness in Toronto. Pediatrics. 2003; 112 e261
- 25 Zhaori G. Antiviral treatment of SARS: Can we draw any conclusions?. CMAJ. 2003; 169 1165-1166
- 26 Hof H, Müller R L, Dörris R. Mikrobiologie-Duale Reihe. 1. Aufl. Stuttgart/D 2000
- 27 Crotty S, Maag D, Arnold J J. The broad-Spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat Med. 2000; 6 1375-1379
- 28 Zhang K W, Ho P L, Ooi G C. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003; 348 1977-1985
- 29 Lee N, Hui D, Wu A. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003; 348 1986-1994
- 30 Peiris J S, Chu C M, Cheng V C. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003; 361 1767-1772
- 31 Zhao Z, Zhang F, Xu M. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J Med Microbiol. 2003; 52 715-720
- 32 Stroher U, DiCaro A, Li Y. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon-alfa. J Infect Dis. 2004; 189 1164-1176
- 33 Cinatl J, Morgenstern B, Bauer G. et al . Glycyrrhizin, an active component of liquorrice roots, and replication of SARS-associated coronavirus. Lancet. 2003; 361 2045-2046
- 34 Mazzulli T, Farcas G A, Poutanan S M. Sevre acute respiratory syndrome-associated corornavirus in lung tissue. Emerge Infect Dis. 2004; 10 20-24
- 35 Knowles S R, Phillips E J, Dresser L. et al . Common adverse events associated with the use of Ribavirin for severe acute respiratory syndrome in Canada. Clin Infect Dis. 2003; 37 1139-1142
- 36 Zhu C M, Cheng V C, Hung I F. Role of Lopinavir/Ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax. 20 004; 59 252-256
- 37 Chan K S, Lai S T, Chu C M. M. Treatment of SARS with Lopinavir/Ritonavir: A multicentre retrospective matched cohort study. Hong Kong Med J. 2003; 9 399-406
- 38 Yamamoto N, Yang R, Joshinaka Y. HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus. Biochem Biophys Res Commun. 2004; 318 719-725
- 39 Barnard D L, Hubbart V D, Burten J. Inhibition of SARS-associated coronavirus (SARSCoV) by calpain inhibitors in beta-D-N4-hydroxycytidine. Antivir Chem Chemother. 2004; 15 15-22
- 40 Li W, Moore M J, Vasilieva N. Angiotensin-converting enzyme is a functional reseptor for the SARS coronavirus. Nature. 2003; 426 450-454
- 41 Huang L, Sexton D J, Skogerson K. novel peptide inhibitors of angiotensin-converting enzyme2. J Biol Chem. 2003; 278 15 532-15 540
- 42 Dales N A, Gould A E, Brown J A. Substrate based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. J Am Chem Soc. 2002; 124 11 852-11 853
- 43 Sui J, Li W, Murakami A. Potent neutralisation of SARS coronavirus by a human mAb to S1 protein that blocks reseptor association. Prog Natl Acad Sci USA. 2004; 101 2536-2541
- 44 Liu S, Xiao G, Chen Y. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet. 2004; 363 938-947
- 45 Kliger Y, Levanon E Y. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy. BMC Microbiol. 2003; 3 20
- 46 Zhang R, Guo Z, Lu J. Inhibiting SARS-associated coronavirus by small interfering RNA. Chin Med J. 2003; 116 1262-1264
- 47 Jacque J M, Triques K, Stevenson M. Modulation of HIV-1 replication by RNA interference. Nature. 2002; 418 435-438
- 48 Kabadia S B, Brideau-Anderson A, Chisari F V. Interference of hepatitis C virus RNA replication by short interfering RNAs. Proc Natl Acad Sci USA. 2003; 100 2014-2018
- 49 Hamasaki K, Nakao K, Mazumoto K. et al . Short interfering RNA-directed inhibition of hepatitis B virus replication. FEBS Lett. 2003; 543 51-54
- 50 Zhang J, Li T, Fu L. Silencing SARS-CoV spike protein expression in cultured cells by RNA interference. FEBS Lett. 2004; 560 141-146
- 51 He M L, Zheng B, Peng Y. Inhibition of SARS-associated coronavirus infection and replication by RNA interference. JAMA. 2003; 290 2665-2666
- 52 Sasaki H, Takai M, Kobajashi M. et al . Effect of Glycyrrhizin, an activ component of liquorrice roots, on HIV replication in cultures of peripheral blood mononuclear cells from HIV-seropositive patients. Pathobiology. 2002; 70 229-236
- 53 Kumada H. Lon-term treatment of chronic hepatitis C with Glycyrrhizin [stronger neo-minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. Oncology. 2002; 62 (suppl 1) 94-100
- 54 Matsuo K, Takenaka K, Chimomura H. Lamivudine and Glycyrrhizin for treatment of chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic HBV carrier with non-hodgkin lymphoma. Leuk Lymphoma. 2001; 41 191-195
- 55 Kim J y, Choi C Y, Lee K J. Induction of inducible nitric oxide synthase and proinflammatory cyrokines expression by o, p'-DDT in macrophages. Toxicol Lett. 2004; 147 261-269
- 56 Keyaerts E, Vijgen L, Maes P. et al .Inhibition of SARS-CoV infection in vitro by S-nitroso-N-acetylpenicillamine, a nitric oxid donor compound. 11th International Congress on Infectious Diseases. Cancun, Mexico March 4 - 7, 2004
- 57 Wu C J, Jan J T, Chen C M. Inhibition of SARS coronavirus replicaton by niclosamide. Antimicrob Agents Chemother. 2004; 48 2693-2696
- 58 Gomersall T D, Kargel M J, Lapinski S E. Pro/Con clinical debate: steroids are a key component in the teratment of SARS. Crit Care. 2004; 8 105-107
- 59 Nicholls J M, Poon L L, Lee K C. Lung pathology of fatal SARS. Lancet. 2003; 361 1773-1778
- 60 Booth T M, Matukas L M, Tomlinson G A. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003; 289 2801-2809
- 61 Hsu L Y, Lee C G, Green J A. SARS in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. 2003; 9 713-717
- 62 Ho J C, Ooi G C, Mok T Y. High-dose pulse versus nonpulse corticosteroid regiments in SARS. Am J Respir Crit Cer Med. 2003; 168 1449-1456
- 63 Wang H, Ding Y, Li X. et al . Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. N Engl J Med. 2003; 349 507-508
- 64 Chan K S, Zheng J P, Mok Y W. SARS: prognosis, outcome and sequelae. Respirology. 2003; 8 (suppl) S36-40
- 65 Hong N, Du X K. Avascular necrosis of bone in SARS. Clin Radiol. 2004; 59 602-608
- 66 Cinatl J R, Michaelis M, Scholz M. et al . Role of interference in the treatment of SARS. Expert Opin Biol Ther. 2004; 4 827-836
- 67 Tan E L, Ooi E E, Lin C Y. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg Infect Dis. 2004; 10 581-586
- 68 Hensley L E, Fritz L E, Jahraling P B. et al . Interferon-β 1a and SARS coronavirus replication. Emerg Infect Dis. 2004; 10 317-319
- 69 Loutfy M R, Blatt L M, Siminovich K A. Intereferon alfacon-1 plus corticosteroids in SARS: a preliminary study. JAMA. 2003; 290 3222-3228
- 70 Haagmanns B L, Kuiken T, Martina B E. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med. 2004; 10 290-293
- 71 Muller M P, McGeer A, Straus S E. et al . Clinical trials and novel pathogens: lessons learned from SARS. Emerg Infect Dis. 2004; 10 389-394
Univ.-Prof. Dr. med. David Groneberg
Zentrum Innere Medizin, Abteilung Pneumologie, Medizinische Hochschule Hannover
Carl-Neuberg-Str. 1 OE6870
30625 Hannover
eMail: groneberg.david@mh-hannover.de