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ArbidolArbidol 2007 - 2005 Studies:

State Key Laboratory of Virology, Institute of Medical Virology, Wuhan University, Wuhan, P.R. China English publication .pdf

Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo

Shi L, Xiong H, He J, Deng H, Li Q, Zhong Q, Hou W, Cheng L, Xiao H, Yang Z.

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 microg/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.

Health UA 10 4 2006 English (professional translation .pdf)

Specific Molecular-Biological Actions of the Antiviral Drug Arbidol

Arbidol is an antiviral drug which is effective against Group A and B influenza strains. The molecular-biological action which distinguishes Arbidol from other drugs is its ability to inhibit viral reproduction in the early stages; the drug acts by changing the regulation of cell metabolism. Arbidol differs from rimantadine in the molecular mechanism of its antiviral action.

Original Russian Document .pdf

Voprosy Virusologii Mar-Apr;51(2):20-2 2006 English (professional translation .pdf)

The efficacy of antiviral preparations in vitro on the reproduction of influenza virus strains A/H5N1, which caused an epizootic among domesticated birds in summer 2005

D. K. Lvov, I. T. Fedyakina, M. Yu. Shchelkanov, A. G. Prilipov, P. G. Deryabin, G. A. Galegov

The commercial drugs rimantadine, amantadine, ribavirin and arbidol are effective in suppressing in in vitro reproduction of highly pathogenic avian influenza A/H5N1 viruses. This study was done on porcine embryo kidney (SPEV) cells and the highly pathogenic A/Duck/Novosibirsk/ 56/05(H5N1) strain from an infected domestic duck (anas platyrhynchos domesticus) in the Lake Chany area, Novosibirsk region.

Original Russian Document .pdf

Journal of Pharmaceutical and Biomedical Analysis 2006, Article In Press English publication .pdf

Determination of arbidol in human plasma by LC-ESI-MS

Xiao Lui, Yu-Wei Huang, Juan Li, Xiao-Bo Li, Kai-Shun Bi, Xiao-Hui Chen

A sensitive, specific and accurate method for determination of arbidol in human plasma was developed. Arbidol and internal standard were extracted from plasma samples by liquid-liquid extraction with diethyl ether. The chromatographic separation was accomplished on a Shiseido C 18 3 pm.m analytical column (100 mm x 2.0 mm i.d.) at a flow rate of 0.3 mL/min isocratically. Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The method had a chromatographic run time of 6 min. and a good linear relationship over the range 1-1000 ng/mL. The limit of quantitation for arbidol in plasma was 1 ng/mL. The intra-day and inter-day precision (R.S.D. %) was lower than 7% and accuracy ranged from 96-105%. The proposed method enables unambiguous identification and quantification of arbidol in vivo and has been successfully applied to study the pharmacokinetics of arbidol in heathy male Chinese volunteers.

Virology Journal 2006, 3:56 doi:10.1186/1743-422X-3-56 English publication .pdf

Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection.

Yury S. Boriskin, Eve-Isabelle Pecheur, Stephen J. Polyak

Arbidol (ARB) is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV) infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 µM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB’s affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

Ter Arkh. 2005;77(8):84-8. English (professional translation .html)

Sensitivity of various influenza virus strains to arbidol. Influence of arbidol combination with different antiviral drugs on reproduction of influenza virus A

Leneva IA, Fediakina IT, Gus'kova TA, Glushkov RG.

AIM: To study antiviral activity of arbidol in relation to various antigenic subtypes of influenza virus isolated from humans; efficacy of arbidol action in combination with adamantanic antiviral drugs, ribavirin and ribamidil on reproduction of influenza virus A (IVA) in cell culture. MATERIAL AND METHODS: The activity of the drugs against viral reproduction was assessed by inhibition of viral antigens expression detected in virus-infected cells using enzyme immunoassay (EIA). RESULTS: Arbidol is just as good as adamantanic drugs, neuraminidase inhibitors, ribavirin and ribamidil by its inhibiting activity in relation to influenza viruses A and B. Arbidol inhibits reproduction of human IVA antigenic strains H1N1, H2N2, H3N2 and remantadin-sensitive and remantadin-resistant strains of influenza virus. Arbidol inhibits reproduction of pathogenic for humans strains of avian influenza virus H5N1 and H9N2, strains H6N1 and H9N2 having internal genes common with H5N1 and H9N2. The inhibiting activity of arbidolin on cell culture viral reproduction enhanced if arbidol was used in combination with amantadine, remantadin, ribavirin and ribamidil. CONCLUSION: Arbidol has a wide spectrum antiviral activity and inhibits reproduction of various antigenic subtypes and remantadin-resistent human IVA, avian viruses H5N1 and H9N2, influenza viruses B and C.

PMID: 16206613 [PubMed - indexed for MEDLINE]

Original Russian Document .pdf

Vopr Virusol. 2005 Nov-Dec;50(6):32-5 English (professional translation .html)

Sensitivity of influenza A/H5 viruses isolated from wild birds on the territory of Russia to arbidol in the cultured MDCK cells

The effect of the antiviral drug arbidol on the reproduction of avian influenza A/H5 viruses was studied in in vitro experiments. The strains were isolated from the wild birds of Eastern Siberia and they were closely related to the 1997-2000 viruses from South-Eastern Asia. Arbidol was shown to exert a selective inhibiting effect on the reproduction of these viruses in the MDCH cell cultures.

PMID: 16408629 [PubMed - in process]

Original Russian Document .pdf

VIROLOGICA SINICA Vol.20 No.2 April 2005 - Full text not available at this time

Inhibitory Effect of Arbidol Hydrochloride on Coxsackievirus B3 Group in vitro

XIONG Hai-rong, YANG Zhan-qiu, LIU Yin-juan, et al

Arbidol hydrochloride Coxsackievirus group B3 Antiviral effect

Abstract: To study the antiviral activity of Arbidol hydrochloride on Coxsackievirus Group B_3 (CVB_3), the antiviral effect of Arbidol hydrochloride were evaluated with virus inhibitory rates by MTT assay and 50% tissue culture infection dose (TCID_(50)) of the supernatant. The results showed that the viral inhibitory rates were up to 75.48%,45.68%,28.90% and 48.27% respectively in interrupting viral biosynthesis group, directly killing virus group, interfering in viral absorption and penetration groups(2h and 8h). In interrupting viral biosynthesis group,Arbidol hydrochloride could significantly inhibit cytopathic effect (CPE) of CVB_3-infected HEp-2 cells, increase survival rates of CVB_3-infected cells in dose dependent manner and decrease viral titers of the supernatant. It indicates that Arbidol hydrochloride has antiviral effect against Coxsackievirus group B3 (CVB_3).

Original Chinese Document .pdf

Emerging Infectious Diseases EID-05-1609 Research 12-Dec-2005 English publication .pdf

Characterization of highly pathogenic avian influenza (HPAI) A subtype H5N1 strains isolated from an outbreak in poultry and wild birds in Western Siberia, July 2005

Lvov, Dmitry; D.I. Ivanovsky Institute of Virology, Virus ecology Prilipov, Alex; D.I. Ivanovsky Institute of Virology, Molecular genetics, et al

Arbidol hydrochloride Coxsackievirus group B3 Antiviral effect

Abstract: Complete genomes of two highly pathogenic avian influenza (HPAI) A (H5N1) strains isolated from wild birds (A/Grebe/Novosibirsk/29/05) and poultry (A/Duck/Novosibirsk/56/05) during an epizootic in 2005 summer in one location in Western Siberia (Novosibirsk region, Russia) were analyzed. These strains had a basic amino acid motif in the hemagglutinin cleavage site characteristic of HPAI influenza. They differed genetically from the H5N1 avian viruses isolated earlier but were closely related in all genes to the H5N1 viruses isolated from wild birds in Qinghai Lake, China, in May 2005. There was slight genetic differences between the two Western Siberian strains (2005) within the PB1, PB2, PA and NP genes (from one to four amino acid substitutions), but both viruses had Lys-627 in PB2 protein, Glu-92 in NS1, Ser-31 in M2 and a 20-mer deletion in the NA gene. Both isolates were sensitive to remantadine, amantadine, ribavirin, arbidol in porcine embryo kidney cell line.

Zh Mikrobiol Epidemiol Immunobiol. 2005 Nov-Dec;(6): 24-8. English (professional translation .html)

Characteristics of the immune status in specific and nonspecific prophylaxis of influenza in elderly persons, March 2005

T. A. Semenenko, E. P. Seikova, T. P. Gotvyanskaya, A. D. Gaidarenko, N. A. Polezhaeva, L. F. Evseeva, O. G. Nikolaeva

The results of the comparative analysis of the immunological effectiveness of the anti-influenza vaccine Vaxigrip, the interferon inductor arbidol and their combination in 125 elderly persons are presented. In the process of investigation, the immunomodulating activity of the preparations under study was noted. This activity was manifested by the increase of the absolute and relative number of cells carrying CD3+, CD4+ and CD16+ markers, but not CD8+, CD19+ or CD25+; normalization of the immunoregulatory index and stimulation of phagocytic function without significant influence on the level of HLA-DR+ expression or on the concentration of the main classes of immunoglobulins. An increase in the frequency of seroconversions and the multiplicity of growth in the titers of specific antibodies to influenza viruses A (H1N1 and H3N2) and B, most pronounced in persons given arbidol along with an anti-influenza vaccine, was established.

PMID: 16438370 [PubMed - in process]

Original Russian Document .pdf

ANTIVIRAL RESEARCH 65 (3): A63-A64 MAR 2005 - Full text not available at this time

The Features of Antiviral Action of Arbidol—Selection and Characterization of Arbidol-resistant Mutants

Irina A. Leneva1, Alexander M. Shuster2, Alan J. Hay3, Robert G. Glushkov1
1Department of Chemotherapy of Infectious Diseases, Center of Chemistry of Drugs-Russian Chemical and Pharmaceutical Institute, Moscow, Russia; 2‘Masterlek’, Moscow, Russia; 3National Institute for Medical Research, London, UK

An antiviral drug arbidol (1-metyl-2-phenyl-thiomethyl
6-bromoindolehydrochloride monohydrate) is widely used for prophylaxis and therapy of influenza A and B in Russia. The study of effect of arbidol on viral replication showed that arbidol inhibited viral reproduction of all antigen subtype of human influenza A and B viruses, avian influenza viruses, possessing H5 and H9, and rimantadine-resistant strains of influenza A viruses. Arbidol demonstrated broad-spectrum antiviral activity against respiratory viruses inhibiting RSV and adenovirus type 3 viral replication in cell culture.

Arbidol was previously shown to inhibit early stage of influenza A virus replication. The studies of the arbidol effect upon replication of panel of reassortants between A/Singapore/1/57(H2N2) and A/Chiken/Germany/27 (Weybridge strain, H7N7) showed that the greater sensitivity of the Weybridge virus to arbidol was determined by the HA gene; there was no correlation between sensitivity to arbidol and any other gene Arbidol-resistant mutants were obtained by passing viruses in MDCK cells in the presence of increasing drug concentrations. Mutants selected for resistance to arbidol promoted membrane fusion at higher pH (0.2–0.4) than wild-type virus. Arbidol inhibited haemolysis induced by the wild-type virus, but did not inhibit the haemolysis induced by arbidol-resistant mutants. To determine the molecular basic of the arbidol-resistance the HA genes of the wild-type and arbidol-resistant mutants were sequenced.

All mutants had amino acid substitutions only in HA2 subunit, but at different positions. The study of the effect of arbidol on conformation of the HA using conformational antibodies showed that arbidol caused conformational change in the structure of HA of wild-type virus, but not in arbidol-resistant mutants. The data indicate that the target of arbidol is the HA and that arbidol increases its stability to low pH-induced changes and as a consequence inhibits membrane fusion during virus infection.

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