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 DOI:
Cite this article as: Shi, L., Xiong, H., He, J. et al. Arch Virol (2007) 152: 1447. doi:10.1007/s00705-007-0974-5 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
Leneva IA, Fedyakina IT, Fadeeva NI, Guskova TA (1996) Effect of a new antiviral drug arbidol on influenza virus replication. Xth International Congress of Virology Aug: 11–16
Leneva, IA, Hay, A 1998 The mechanism of action of arbidol against influenza virus: selection and characterization of arbidol-resistant mutants Antiviral Res 37 89 Google Scholar Li, Yaolan, Paul, PH 2005 Antiviral activity and mode of action of caffeoylquinic acids from Schefflera heptaphylla (L.) Fordin Antiviral Res 68 1 9 PubMed CrossRef Google Scholar Maitreyi, RS, Broor, S, Kabra, SK 2000 Rapid detection of respiratory viruses by centrifugation enhanced cultures from children with acute lower respiratory tract infections J Clin Virol 16 41 47 PubMed CrossRef Google Scholar Markland, W, Mcquaid, TJ, Jain, J, Kwong, AD 2000 Broad-spectrum antiviral activity of the IMP dehydrogenase inhibitor VX-497: a comparison with ribavirin and demonstration of antiviral additivity with alpha interferon Antimicro Agents Chemother 44 859 866 CrossRef Google Scholar Marshall, NJ, Goodwin, CJ, Holt, SJ 1995 A critical assessement of the use of microculture tetrazolium assays to measure cell growth and function Growth Regulation 5 69 84 PubMed Google Scholar Monobe, H, Ishibashi, T, Nomura, Y, Shinogami, M, Yano, J 2003 Role of respiratory viruses in children with acute otitis media Int J Pediatr Otorhinolaryngol 67 801 806 PubMed CrossRef Google Scholar Mosmann, T 1983 Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity assays J Immunol Methods 65 55 63 PubMed CrossRef Google Scholar Munoz, FM, Galasso, GJ, Gwaltney, JM, Hayden, FG, Murphy, B, Webster, R, Wright, P, Couch, RB 2000 Current research on influenza and other respiratory viruses: II. International Symposium Antiviral Res 46 91 124 PubMed CrossRef Google Scholar Papadopoulos, NG, Bates, PJ, Bardin, PG, Papi, A, Leir, SH, Fraenkel, DJ 2000 Rhinoviruses infect the lower airways J Infect Dis 181 1875 1884 PubMed CrossRef Google Scholar Patel, DD, Kapoor, A, Ayyagari, A, Dhole, TN 2004 Development of a simple restriction fragment length polymorphism assay for subtyping of coxsackie B viruses J Virol Methods 120 167 172 PubMed CrossRef Google Scholar Reed, LJ, Muench, HA 1938 A simple method of estimating fifty percent endpoints Am J Hyg 27 493 497 Google Scholar Schulman, J 1968 Effect of L-amantanamine hydrochloride(amantadine HCL) and methyl-L-adamantanethylamine hydrochloride (rimantadine HCL) on teansmission of influenza virus infection in mice Proc Soc Exp Biol Med 128 1173 1178 Google Scholar Sudo, K, Miyazaki, Y, Kojima, N, Kobayashi, M, Suzuki, H, Shintani, M, Shimizu, Y 2005 YM-53403, a unique anti-respiratory syncytial virus agent with a novel mechanism of action Antiviral Res 65 125 131 PubMed CrossRef Google Scholar Thompson, WW, Shay, DK, Weintraub, E, Brammer, L, Cox, N, Anderson, LJ, Fukuda, K 2003 Mortality associated with influenza and respiratory syncytial virus in the United States JAMA 289 179 186 PubMed CrossRef Google Scholar
World Health Organization (WHO) (2004) World Health Organization: Influenza.
http://www.who.int/mediacentre/factsheets/2003/fs211/en/ Wyde, PR 1998 Respiratory syncytial virus (RSV) disease and prospects for its control Antiviral Res 39 63 79 PubMed CrossRef Google Scholar Xiang, X, Qiu, D, Chan, KP, Chan, SH, Hegele, RG, Tan, WC 2002 Comparison of three methods for respiratory virus detection between induced sputum and nasopharyngeal aspirate specimens in acute asthma J Virol Methods 101 127 133 PubMed CrossRef Google Scholar Zarubaev, VV, Slita, AV, Krivitskaya, VZ, Sirotkin, AK, Kovalenko, AL, Chatterjee, NK 2003 Direct antiviral effect of cycloferon (10-carboxymethyl-9-acridanone) against adenovirus type 6 in vitro Antiviral Res 58 131 137 PubMed CrossRef Google Scholar