Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo
Article First Online: 14 May 2007 Received: 09 December 2006 Accepted: 18 March 2007 Summary
Arbidol, ethyl-6-bromo-4-[(dimethylamino)-methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-in dole-3-carboxylate hydrochloride monohydrate, is an antiviral chemical agent. In this report, we studied the antiviral activity of arbidol against a panel of human respiratory viruses, namely influenza A virus (FLU-A, A/PR/8/34 H1N1), respiratory syncytial virus (RSV), human rhinovirus type 14 (HRV 14), coxsackie virus B3 (CVB3) and adenovirus type 7 (AdV-7)
in vitro in cell culture. Arbidol was found to present potent inhibitory activity against enveloped and non-enveloped RNA viruses, including FLU-A, RSV, HRV 14 and CVB3 when added before, during, or after viral infection, with 50% inhibitory concentration (IC 50) ranging from 2.7 to 13.8 µg/ml. However, arbidol showed selective antiviral activity against AdV-7, a DNA virus, only when added after infection (therapeutic index (TI) = 5.5). Orally administered arbidol at 50 or 100 mg/kg/day beginning 24 h pre-virus exposure for 6 days significantly reduced mean pulmonary virus yields and the rate of mortality in mice infected with FLU-A (A/PR/8/34 H1N1). Our results suggest that arbidol has the ability to elicit protective broad-spectrum antiviral activity against a number of human pathogenic respiratory viruses. References Anonymous, 1999 Arbidol Drugs R&D 2 171 172 Google Scholar Boriskin, YS, Pecheur, EI, Polyak, SJ 2006 Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection Virol J 3 56 PubMed CrossRef Google Scholar Brooks, MJ, Sasadeusz, JJ, Tannock, GA 2004 Antiviral chemotherapeutic agents against respiratory viruses: where are we now and what’s in the pipeline? Pulmonary Med 10 197 203 CrossRef Google Scholar Burger, RA, Billingsley, JL, Huffman, JH, Bailey, KW, Kim, CU 2000 Immunological effects of the orally administered neuraminidase inhibitor oseltamivir in influenza virus-infected and uninfected mice Immunopharmacology 47 45 52 PubMed CrossRef Google Scholar Chai, H, Zhao, Y, Zhao, C, Gong, P 2006 Synthesis and in vitro anti-hepatitis B virus activities of some ethyl-6-bromo-5-hydroxy-1H-indole-3-carboxylates Bioorg Med Chem 14 911 917 PubMed CrossRef Google Scholar Fedyakina, IT, Lenyova, IA, Yamnikova, SS, Glushkov, RG 2005 Sensitivity of influenza A/H5 viruses isolated from wild birds on the territory of Russia to arbidol in the cultured MDCK cells Vopr Virusol 50 32 35 Google Scholar Fleming, DM, Cross, KW 1993 Respiratory syncytial virus or influenza Lancet 324 1507 1510 CrossRef Google Scholar Garozzo, A, Cutri, CC, Castro, A, Tempera, G, Guerrera, F, Sarva, MC, Geremia, E 2000 Anti-rhinovirus activity of 3-methylthio-5-aryl-4-isothiazolecarbonitrile derivatives Antiviral Res 45 199 210 PubMed CrossRef Google Scholar Gern, JE, Busse, WW 1999 Association of rhinovirus infections with asthma Clin Microbiol Rev 12 9 18 PubMed Google Scholar Guskova, TA, Leneva, IA, Fedyakina, IT, Chistyakov, VV, Glushkov, RG 1999 Arbidol kinetics and its effect on influenza A virus replication in MDCK cell culture Chemico Pharmaceut J 6 14 17 Google Scholar Hayden, FG, Atmar, RL, Schilling, M, Johnson, C, Poretz, D, Paar, D, Huson, L, Ward, P, Mills, RG 1999 Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza N Engl J Med 341 1336 1343 PubMed CrossRef Google Scholar Hayden, FG, Belshe, RB, Villaneueva, C, Lanno, R, Hughes, C, Small, I, Dutkowski, R, Ward, P, Carr, J 2004 Management of influenza in households: a prospective randomized comparison of oseltamivir treatment with or without post-exposure prophylaxis J Infect Dis 189 440 449 PubMed CrossRef Google Scholar Kaiser, L, Wat, C, Mills, T, Mahoney, P, Ward, P, Hayden, F 2003 Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations Arch Intern Med 163 1667 1672 PubMed CrossRef Google Scholar Kiso, M, Mitamura, K, Sakai-Tagawa, Y, Shiraishi, K, Kawakami, C, Kimura, K, Hayden, F, Sugaya, N, Kawaoka, Y 2004 Resistant influenza A viruses in children treated with oseltamivir: descriptive study Lancet 364 759 765 PubMed CrossRef Google Scholar Kneyber, MCJ, Moll, HA, Groot, RD 2000 Treatment and prevention of respiratory syncytial virus infection Eur J Pediatr 159 399 411 PubMed CrossRef Google Scholar
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