Arbidol

[Iwonder]

Title Arbidol: A Broad-Spectrum Antiviral Compound that Blocks Viral Fusion.

Author(s) Boriskin YS, Leneva IA, Pécheur EI, Polyak SJ
Institution Virology 359690, University of Washington, 325 9th Avenue, Seattle, Washington 98104-2499, USA. polyak@u.washington.edu.

Source Curr Med Chem 2008; 15(9):997-1005.

Abstract Arbidol (ARB; ethyl-6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-indole-3-carboxylate hydrochloride monohydrate), is a Russian-made potent broad-spectrum antiviral with demonstrated activity against a number of enveloped and non-enveloped viruses. ARB is well known in Russia and China, although to a lesser extent in western countries. Unlike other broad-spectrum antivirals, ARB has an established molecular mechanism of action against influenza A and B viruses, which is different from that of available influenza antivirals, and a more recently established mechanism of inhibition of hepatitis C virus (HCV). For both viral infections the anti-viral mechanism involves ARB inhibition of virus-mediated fusion with target membrane and a resulting block of virus entry into target cells. However, ARB inhibition of fusion exploits different ARB modalities in case of influenza viruses or HCV. This review aims to summarize the available evidence of ARB effects against different groups of viruses, also, to compare various aspects of ARB anti-fusion mechanisms against influenza virus and HCV (with reference to different stringency of pH-dependence of these two viral fusogens) and to discuss further prospects for ARB and its improved derivatives of the parent compounds.

Language English

Pub Type(s) Journal Article

PubMed ID 18393857

http://www.unboundmedicine.com/medline/ebm/record/18393857/full_citation/Arbidol:_A_Broad_Spectrum_Antiviral_Compound_that_Blocks_Viral_Fusion_

More studies can be read at : http://www.arbidol.org/

[JJackson]

Re: Arbidol

My journal access is not letting me view the full text has anyone read this if so please give us your views.

[JJackson]

Re: Arbidol

Arbidol has a Wikipidia page here and from that, on external links, to a arbidol.org including this article
The sensitivity of various influenza virus strains to arbidol. The influence of arbidol in combination with other antiviral drugs on reproduction of influenza virus A.

Aim. To study the antiviral activity of arbidol in relation to various antigen subtypes of influenza virus; to study the effectiveness of arbidol when used in combination with adamantine-type antiviral drugs, ribavirin and ribamidil in inhibiting influenza virus reproduction in cell culture.
Material and Methods. The activity of the drugs against viral reproduction was assessed according to the expression of viral antigens in virus-infected cells, determined by enzyme immunoassay.
Results. Arbidol is just as good as adamantine drugs, neuraminidase inhibitors, ribavirin and ribamidil in its inhibiting effect on influenza virus A and B. Arbidol inhibits reproduction of human IVA antigen strains H1N1, H2N2, H3N2 and rimantadine-sensitive as well as rimantidine-resistant strains of the influenza virus. Arbidol inhibits the reproduction of strains of avian influenza, pathogenic to humans, H5N1 and H9N2, and H6N1 and H9N2, which have genes in common with H5N1 and H9N2. Arbidol?s inhibitory effect on viral reproduction in cell culture was enhanced when it was used in combination with amantidine, rimantadine, ribavirin and ribamidil.
Conclusion. Arbidol has broad-spectrum antiviral action, and inhibits reproduction of various antigenic subtypes and rimantadine-resistant human IVA, avian viruses H5N1 and H9N2, and influenza viruses B and C.

[gsgs]

Re: Arbidol

is any country (Russia ?) stockpiling Arbidol or Triazoverin
or such for a possible pandemic ?

I only heard of Tamiflu and Relenza stockpiles, but read about many
other drugs claimed to be of similar efficiency.
And now we have widespread resistance to Tamiflu in H1N1.

[gsgs]

Re: Arbidol

http://www.ncbi.nlm.nih.gov/pubmed/19227120?ordinalpos=55&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

The Ingavirin efficacy was comparable with that of Remantadine, markedly exceeded that of Arbidol and was lower than that of Tamiflu.

[gsgs]

Re: Arbidol

http://www.ncbi.nlm.nih.gov/pubmed/19227120?ordinalpos=55&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

1: Antibiot Khimioter. 2008;53(7-8):27-30. Links
[Therapeutic efficacy of Ingavirin, a new domestic formulation against influenza A virus (H3N2)]
[Article in Russian]


Loginova SIa, Borisevich SV, Maksimov VA, Bondarev VP, Nebol'sin VE.
Investigation of the therapeutic efficacy of Ingavirin (Valenta Farmacevtica, Russia) against influenza virus A (H3N2) vs. Tamiflu, Remantadin and Arbidol showed that in daily doses of 15 and 20 mg/kg (equal by the efficacy to the human doses of 90 and 120 mg) Ingavirin was effective in protection of the albino mice infected by the virus in a dose of 10 to 15 LD50. The protective efficacy was 38.3-39.2% and the increase of the average lifespan amounted to 4.2-4.4 days. The Ingavirin efficacy was comparable with that of Remantadine, markedly exceeded that of Arbidol and was lower than that of Tamiflu. Investigation of the Ingavirin influence in doses of 15 and 20 mg/kg on the dynamics and level of the influenza virus A/Aichi/2/68 reproduction in the lungs of the infected albino mice weighing 10-12 g revealed that during the whole observation period in the doses tested Ingavirin was effective in inhibition of the influenza virus reproduction. During the whole period of the observation (5 days) Ingavirin was effective in inhibiting the formation of the virus specific hemagglutinin in the target organ.

[Anne]

Re: Arbidol

The Ingavirin efficacy was comparable with that of Remantadine, markedly exceeded that of Arbidol and was lower than that of Tamiflu

[gsgs]

Re: Arbidol

...in albino mice

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1: Ter Arkh. 2009;81(3):51-4.
[Efficacy of ingavirin in adults with influenza][Article in Russian]


[No authors listed]
AIM: To compare therapeutic efficacy and safety of ingavirin and arbidol in patients with influenza. MATERIAL AND METHODS: The trial included 105 patients with a verified diagnosis of influenza, definite clinical symptoms, body temperature at least 38 degrees C and duration of the disease 36 hours maximum. Ingavirin efficacy was analysed basing on the evidence for 100 patients with uncomplicated influenza. The patients were randomized into three groups: taking ingavirin in a single daily dose 90 mg (n = 33), placebo (n = 36) or arbidol (200 mg 4 times a day). The duration of the treatment was 5 days. RESULTS: Intake of ingavirin in initial 24-36 hours of the disease significantly reduced fever compared to placebo and arbidol (34.5, 72.0 and 48.4 hours, respectively). Ingavirin was less toxic and had no side effects. CONCLUSION: Ingavirin is safe and effective in the treatment of influenza. By some criteria it is more effective than arbidol.

PMID: 19459424 [PubMed - in process

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http://www.ncbi.nlm.nih.gov/pubmed/19446151?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Conclusion: In this study in healthy Chinese male volunteers, the dispersible tablet formulation and the 200-mg capsule formulation of arbidol met the SFDA's regulatory definition of bioequivalence based on the rate and extent of absorption.

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http://www.ncbi.nlm.nih.gov/pubmed/19028526?ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

ARB-resistant mutants, selected from the most sensitive reassortant, possessed single amino acid substitutions in the HA2 subunit which caused an increase in the pH of fusion and the associated conformational change in HA. ARB was shown to stabilize the HA by causing a 0.2 pH unit reduction in the pH of the transition to the low pH form, which was specifically abrogated by the resistance mutations. Some of the resistance mutations, which reduce acid stability and would disrupt ARB-HA interactions, are located in the vicinity of a potential ARB binding site

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1: Antibiot Khimioter. 2008;53(3-4):13-7. Links
[Viferon suppositories in the treatment of influenza in adults]
[Article in Russian]


Gatich RZ, Kolobukhina LV, Vasil'ev AN, Isaeva EI, Burtseva EI, Orlova TG, Voronina FV, Kol'tsov VD, Malinovskaia VV.
One hundred and one patients at the age of 18 to 60 years suffering from influenza were observed during increased ratio of the sickness due to the influenza virus types A (H1N1 and H3N2) and B. The diagnosis of influenza was confirmed by the laboratory tests. Viferon was used in the treatment of 35 patients. The randomized double blind placebo-controlled study revealed high therapeutic efficacy ofviferon and its immunomodulating effect on the T-cells, the neutrophil phagocytic activity and the decrease of the levels of the circulating immune complexes. Viferon and arbidol decreased the fever periods and the toxicosis symptoms vs. the placebo. The therapeutic efficacies of viferon and arbidol were on the whole comparable, whereas the clinical findings and the results of the immunological tests were evident of the viferon higher therapeutic and immunomodulating efficacy. No side effects of the drugs were recorded. The tolerability was excellent. Viferon can be recommended for the treatment of influenza in adults.

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Evaluation of the efficacy of wiferon and arbidol in adult influenza][Article in Russian]


Kolobukhina LV, Malinovskaia VV, Gatich RZ, Merkulova LN, Burtseva EI, Isaeva EI, Parshina OV, Guseva TS, Orlova TG, Voronina FV.
The therapeutic efficacy of wiferon (recombinant alpha2beta-interferon) versus arbidol was studied in a double-blind controlled study in patients with laboratorily verified influenza. Within the first 24-36 hours after the onset of the disease, wiferon and arbidol reduced the duration of fever, intoxication, and the catarrhal symptoms of the disease as a whole. The agents were shown to have an immunomodulating effect.

PMID: 18318133 [PubMed - indexed for MEDLINE]

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The study of the activity of arbidol against epidemic influenza A and B virus strains (2002-2005) in the cultured MDCK cells showed the higher sensitivity of enzyme immunoassay than that of hemagglutination test. The influenza A virus strains tested, including those resistant to rimantadine (5 microg/ml), were sensitive to arbidol (10 microg/ml). The population of influenza B virus strains was heterogeneous in this indicator, 43% of the strains being less sensitive to arbidol.

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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.

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[gsgs]

Re: Arbidol

http://thisbluemarble.com/showthread.php?t=14241

[gsgs]

Re: Arbidol

ingavirin showed that this agent was less effective than arbidol

http://www.ncbi.nlm.nih.gov/pubmed/20608077