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-pheny l-thiomethy l
-3-carbotoxy- 4-dimetylaminomethyl- 5-hydroxy-
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.
Voen Med Zh. 2004 Sep;325(9):44-5, 80. English (professional tanslation .pdf)
Arbidol used in the prophylaxis of acute respiratory viral infections and their complications in servicemen
Shuster AM, Shumilov VI, Shevtsov VA, Mar'in GG, Kozlov VN.
The prophylactic action of arbidol to prevent the acute respiratory viral
infections and their complications (extra-hospital pneumonia) was studied under conditions of two
military collectives during winter and summer time. The data obtained confirm the prophylactic activity
of the drug in respect of acute respiratory viral infections. Regardless of the degree of disease epidemic
rise among the servicemen who didn't take arbidol the minimal threshold of influenza and other acute
respiratory viral infections incidence (10-15%) remained in the experimental group. The incidence of
pneumonia decreased. It was connected with decrease in viral-and-bacterial pneumonia. The number
of patients with bacterial (generally pneumococcal) pneumonia didn't change.
PMID: 15537102 [PubMed - indexed for MEDLINE]
Original Russian Document .html
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2004 Jun;26(3):289-93.
Efficacy and safety of arbidol in treatment of naturally acquired influenza
Wang MZ, Cai BQ, Li LY, Lin JT, Su N, Yu HX, Gao H, Zhao JZ, Liu L.
Department of Respiratory Disease, PUMC Hospital, CAMS and PUMC, Beijing 100730, China. email@example.com
OBJECTIVE: To evaluate the efficacy and safety of Arbidol in the treatment of naturally acquired influenza. METHODS: A randomized,
double-blinded, placebo controlled trial was conducted. Subjects were enrolled. The inclusion criteria included: aged 18 to 65 years, presented within 36 hours
of onset of influenza symptoms; and had documented temperature of 37.8 degrees C or higher during an influenza outbreak in the community. Individuals were
randomly divided Arbidol group (200 mg three times daily for 5 days) or placebo group.
RESULTS: Totally 232 individuals were recruited and received medication
and follow-up. All of them were qualified to be analyzed for safety as intent-to-treat population (ITT) (113 Arbidol, 109 placebo). Twenty-two (9.48%) were during
follow-up or refused to continue the trial, and 210 completed as scheduled and identified as PP population (102 Arbidol, 108 placebo). Totally 125 individuals were
identified as influenza-infected through laboratory test, which was defined as PPi population (59 Arbidol, 66 placebo). In PPi population, the cumulative alleviation
proportion of Arbidol group was significantly higher than that of placebo group. The median duration of illness was 72.0 hours (95% confident interval (CI) 66.00-78.00
hours) in Arbidol group and 96.0 hours (95% CI 87.46-104.54 hours) in placebo group. The median area under the curve (AUC) of decreased total score were significantly
higher in Arbidol group than in placebo group, which were 780.00 and 684.00 score-hours respectively. For PP population, similar results were seen. Adverse events
reported were similar in Arbidol group and in placebo group. The main adverse events were gastrointestinal symptoms and increased transaminase.
CONCLUSION: Arbidol was effective and well tolerated in the treatment of early naturally acquired influenza.
PMID: 15266832 [PubMed - indexed for MEDLINE]
Original Chinese Document (3mb .pdf)
Chinese Pharmacological Bulletin 2004 Vol.20 No.10 P.1150 - 1152
Arbidol hydrochloride Pharmacodynamic study of anti-influenza virus infection
Sun Yan-chi, ZHANG Shu-qin LIU Zhi-yi Liu Jianwei Jinyuqin
Study about pharmacodynamics of arbidol hydrochloride on Influenza virus infection
Abstract Objective : To investigate the effects of the anti-influenza virus Arbidol role. Methods vivo, in vitro
model of influenza virus. Application for a certain concentration of hydrochloric acid in vitro Arbidol role in the influenza A virus subtype
H1N1 infection of host cells. To investigate the use of CPE and the cell viability was measured by MTT assay; hydrochloric acid in vivo
application for the treatment of influenza virus infection in mice Arbidol model Index changes in the lung. Arbidol hydrochloride results
in vivo, In vitro anti-influenza viruses have the same effect. Conclusion Arbidol hydrochloride is a good anti-virus drugs.
Keywords : Arbidol hydrochloride; The influenza virus; Pharmacodynamics "Key words : School Offic
Author : Jinyuqin (1979-), female, master's degree students, research direction : virology; Sun - (1958-) male,
master's, professors and research directions : virology, communications authors Tel:0431-5619389, Fax : 0431-5650634, E-mail : firstname.lastname@example.org
The goal : Jinyuqin (Regenerative Medicine Institute of Science Laboratory at Jilin University, Jilin, Changchun 130021)
Sun - (Regenerative Medicine Institute of Science Laboratory at Jilin University, Jilin, Changchun 130021)
Shuqin (Regenerative Medicine Institute of Science Laboratory at Jilin University, Jilin, Changchun 130021)
Shu-qin LIU Zhi-yi (Regenerative Medicine Institute of Science Laboratory at Jilin University, Jilin, Changchun 130021)
Liu Jianwei (Regenerative Medicine Institute of Science Laboratory at Jilin University, Jilin, Changchun 130021)
Yan Qi (Changchun College of Respiratory Medicine, Jilin, Changchun 130021)
 Zhong Bin, Wang Sheng, , Sun et al. influenza in Thailand have anti-influenza virus activity of mouse model et al. Biotechnology Communications, 2000,11 (2) : 81-5.
Gushkov RG, Gus Kovacevic TA, Krylova. Nikolaeva IS.Mechanisms of arbid-ole 's immunomodulating action[J]. Vestn Ross Akad Med Nauk. 1999, (3) : 36-40.
Drinevskii VP, Osidak LV. Natsina VK et al.Chemotherapeutics for treatment of Influenza and other viral respiratory tractinfaction in child-ren[J]. AntibiotKhimioter. 1998,43 (9) : 29-34.
Shumilov VI, Shuster AI. Lobastov SP et al.Efficiency of arbidol in prophylaxic and treatment of respiratory viral infections in servicement[J] acut. Voen MedZh. 2002,323 (9) : 51-3,96.
 Wen-dong. Cell proliferation was measured by a colorimetric method, and quickly decay et al. The chemistry of life, 1994,14 (6) : 44-6.
[Du Ping Zhu Guan, editor et al. Modern clinical virology [M], Beijing : People's Medical Publishing House. 1991:563.
Received Date : January 12, 2004
Xiu draft Date : March 3, 2004
Publication date : October 20, 2004
RMZH,Volume 11 No. 21, 2003 English (babblefish .html)
Experience of the application of Arbidol with treatment and preventive maintenance of influenza and ORVI in children in the Ukraine
S.A. Kramarev, L.A. Is chamber National medical university, Kiev, the Ukraine
Influenza and sharp respiratory virus infections (ORVI) are the diseases most common in the Ukraine. Yearly in the country are recorded
tens of millions of cases ORVI, millions of days of disablement, passages of school, connected with them. Economic damage from the influenza only composes about
400 million 10 kopecks per year [ 6 ]. During only one first calendar quarter after the medical aid apropos of influenza and ORVI in the Ukraine they are turned
to 10 million people, among whom 52% comprise the children. The level of morbidity ORVI exceeds the same of all remaining infections among the children 7-7.5 times.
A quantity of sick ORVI of children is 1.5-3.0 times more than adult . For the children the influenza and ORVI are most dangerous. At this age most frequently
are encountered the defeats of central nervous system, from the light neurologic disorders to the heavy defeats of brain, such complications as bronchitis, pneumonia,
acute average otitis are recorded in each third child, sick with influenza and ORVI. The younger the child, the greater he has the probability of the development of
complications. This probability decreases by 20% each of the subsequent 6 years of the life of child [ 11 ]
V.I. Litus, The Ukraine Kiev medical academy of graduate formation
Original Russian Document .html
Voen Med Zh. 2002 Sep;323(9):51-3, 96. - Full text not available at this time
Efficacy of arbidol in prophylaxis and treatment of acute respiratory viral infections in servicemen
Shumilov VI, Shuster AM, Lobastov SP, Shevtsov VA, Mednikov BL, Piiavskii SA, Litus VI.
The authors present the results of study of arbidolum therapeutic-and-prophylactic effectiveness
in acute respiratory viral infections (ARVI) under conditions of military staff with determination of economic expediency.
Coefficient of effectiveness of arbidolum prophylactic use was 25% and efficiency index--1.33. In experimental group the ARVI
complicated forms were noted in 3% of the patients and in control group--in 5%. Due to decreased expenses on the treatment of
non-complicated and complicated ARVI forms the cost of therapy of one servicemen in the first group was 290.6 rubles, in the
second group--323 rubles, in the third group--336 rubles and in the fourth group--368 rubles. The results of investigation have
shown the significant advantage of arbidolum therapeutic-and-prophylactic use compared with other variants. Its use permitted
to decrease the febrile period, to reduce the manifestation of symptoms of intoxication and affection of upper respiratory tract.
PMID: 12449757 [PubMed - indexed for MEDLINE]
RMZH,Volume 11 No. 12 2002 English (babblefish .html)
The molecular-biological special features of the action of Arbidol the new antiviral preparation
Arbidol, the new antiviral preparation, effective with respect to the viruses of influenza A and B. the Molecular- biological
special features of the action of Arbidol are determined by its ability to suppress the reproduction of virus at the early stages, the action of
preparation realizes with a change in the regulation of cellular metabolism. Preparation is differed from remantadine in the molecular mechanism of antiviral action.
Arbidol Military Study English (babblefish .html) (or .pdf)
REPORT on the program of the estimation of the effectiveness of the medicine of "Arbidol"
in the preventive maintenance and the treatment of influenza and sharp respiratory virus infections in soldiers.
The problem of acute respiratory diseases for the military associations with the high risk of
the development of the infections of the respiratory tract is especially urgent. In particular, in the newly formed parts,
training centers, parts from the composition of united groupings of troops in the local military conflicts and the peacemaking
forces. Under the contemporary conditions respiratory diseases are predominantly the infections of those organized associations,
where the conditions determine the activity of the mechanism of the transfer of agents and the heterogeneity of the composition
of people. As the starting gear of the making more active of epidemic process with ORZ in the military associations serves their
renovation. As proof serve lifts in the annual dynamics of morbidity connected with the calls in VS RF.
Use in the real practice of the developed positions on an improvement in the quality of preventive
maintenance and treatment of sharp respiratory infections with the use of arbidol makes it possible to decrease morbidity, to
increase the effectiveness of therapeutic measures and to optimize the expenditures, connected with the acute respiratory diseases in soldiers.
Vopr Virusol. 2002 Mar-Apr;47(2):42-5. - Full text not available at this time
Study of the effect of antiviral drugs on the reproduction of the respiratory syncytial virus by enzyme immunoassay
Leneva IA, Sokolova MV, Fediakina IT, Khristova ML, Fadeeva NI, Gus'kova TA.
A test system based on EIA was developed for evaluating the efficiency of drugs active towards the respiratory syncytial
virus (RSV) in cell culture. Virasole and its structural analog ribamedii active towards RSV infection and arbidol whose activity in RSV infection
is unknown were tested. Like virasole and ribamedil, arbidol inhibited the expression of RSV antigens, the inhibitory effect increasing with the drug
concentration and decreased with increase of the multiplicity of virus infection. MIC50 for arbidol, virasole, and ribamedil were 10, 5, and 6 micrograms/ml,
respectively. These data prompt clinical trials of arbidol in RSV infection.
PMID: 12046469 [PubMed - indexed for MEDLINE]
Arbidol Prophylatic Study English (babblefish .html) (or .pdf)
Study of epidemiological effectiveness in the application of domestic preparation of "arbidol" for preventive maintenance
and treating the sharp respiratory virus infections in Moscow
At present there does not exist vaccine preparations against the urgent agents of respiratory infections (with exception
of influenza vaccines), which contributes to the maintenance of the morbidity of adult and children's population at the high level. In connection with
this to completely regularly accentuate attention to the study of epidemiological effectiveness and the application of effective means of the unspecific
preventive maintenance of sharp respiratory virus infections (ORVI).
One of the methods of solution of the problem indicated is the search for the preparations, which combine antiviral activity
with the immunostimulating properties. Unspecific preventive maintenance is shown to people with the clinical signs of the decreased resistance of
the organism: _ frequent respiratory disease with protracted or complicate flow; by the presence of the chronic centers of infections; by severe chronic
somatical illnesses. Not is less urgent unspecific preventive maintenance ORVI among the contingents of the risk, which include medical workers, who
are, in view of the specific character of their activity, those not only by most subjected to the risk of infection, but also the source of infection for the
patients with respect to these infections.
The preformed form of preparation makes it possible to use it in the dispensary- polyclinical network for the mass preventive
maintenance in the period of seasonal and mass lift.
"RMZH,Volume 9 No.16-17, 2001" English (babblefish .html)
Study of the immunomodulating activity of Arbidol
K.m.n. YE.P. Sel'kova, I.YU. Gracheva, k.m.n. T. P g.otvyan.chk.aya, Danilin's k.m.n. G.A., k.m.n. M.P. Amaryan, d.m.n. T.A. Semenenko GKB im. S.P. of Botkin, GKB ? 3, g. Zelenograd
At present there does not exist vaccine preparations against the urgent agents of sharp respiratory virus infections (ORVI) (with exception of influenza vaccines), which contributes to the
maintenance of morbidity at the high level. In connection with this to completely regularly accentuate attention to the approval and application of new effective means of unspecific preventive maintenance ORVI. One
of the methods of solution of the problem indicated is the search for the preparations, which combine antiviral activity with the immunostimulating properties. Unspecific preventive maintenance is shown to people with
the clinical signs of the decreased resistance of the organism: _ frequent respiratory disease with protracted or complicate flow; by the presence of the chronic centers of infections; by severe chronic somatical
illnesses [ 1 ]. Not is less urgent unspecific preventive maintenance ORVI among the medical workers, in view of the specific character of its activity who are the group of professional risk.
The purpose of the present investigation was the study of the immunomodulating activity of the domestic preparation of arbidol, created in the Center for chemistry of medicines - All-Russian scientific research
chemicopharmaceutical institute (VNIKHFI - ALL-UNION SCIENTIFIC RESEARCH CHEMICAL AND PHARMACEUTICAL INSTITUTE IM. SERGO ORDZHONIKIDZE); and permitted Farmkomitetom MZ RF to the clinical application in adult [ 2 ].
Antiviral Chemistry & Chemotherapy 10:155–185 English publication .pdf
Approaches and strategies for the treatment of influenza virus infections
Joseph M Colacino, Kirk A Staschke, and W Graeme Laver
Influenza A and B viruses belong to the Orthomyxoviridae family of viruses. These viruses
are responsible for severe morbidity and significant excess mortality each year. Infection with
influenza viruses usually leads to respiratory involvement and can result in pneumonia and
secondary bacterial infections. Vaccine approaches to the prophy-laxis of influenza virus infections
have been problematic owing to the ability of these viruses to undergo antigenic shift by
exchanging genomic segments or by undergoing antigenic drift, consisting of point mutations in
the haemagglutinin (HA) and neuraminidase (NA) genes as a result of an error-prone viral
polymerase. Historically, antiviral approaches for the therapy of both influenza A and B viruses
have been largely unsuccessful until the elucidation of the X-ray crystallographic structure of the
viral NA, which has permitted structure-based drug design of inhibitors of this enzyme. In addition,
recent advances in the elucidation of the structure and complex function of influenza HA
have resulted in the discovery of a number of diverse compounds that target this viral protein.
This review article will focus largely on newer antiviral agents including those that inhibit the
influenza virus NA and HA. Other novel approaches that have entered clinical trials or
been considered for their clinical utility will be mentioned.
Arbidol Childrens Study English (babblefish .html) (or .pdf)
REPORT "Arbidol in the preventive maintenance of the influenza and other sharp respiratory virus infections in children at the age is older than 6 years".
Sharp respiratory infections relate to the number of most extended diseases of man and compose half or more from
the total number of acute diseases (Pilar Orine F.J. and co-auth., 1998). As early as 1979 by the World Health Organization (WHO - WORLD HEALTH
ORGANIZATION) it was recomended to the scientific research associations focus first priority attention on the development of the effective methods
of preventive maintenance and timely diagnostics of respiratory pathology in children. After practically quarter of century the problem of respiratory
infections in children became even more urgent. The diseases of the organs of respiration - most frequent pathology in children (Kagans S.YU. and
co-auth., 1998), which specifies the expediency to isolate sharp respiratory infections into the separate group of the diseases of respiratory system.
The results of epidemiological studies attest to the fact that on the average each child transfers from 3 to 5 episodes ORZ per year (Korovin N.A. and co-auth., 1998).
Obtained data clinically base the expediency of using Arbidol with the therapeutic and prophylactic purpose in the categories of children being
investigated and are the basis of the guarantee of a data base for further estimated studies in the real practice.
Antibiot Khimioter. 1998;43(9):29-34. English (professional tanslation .html) (or .pdf)
Chemotherapeutics for treatment of influenza and other viral respiratory tract infections in children
Drinevskii VP, Osidak LV, Natsina VK, Afanas'eva OI, Mil'kint KK, Danini GV, Ispolatova AV, Koreniako IE,
Karelina NN, Marinich IG, Boldasov VK.
Research Institute of Grippe, Russian Academy of Medical Sciences, St. Petersburg.
Therapeutic efficacy of remantadine and arbidole was studied in the clinical and laboratory
observation of pediatric in- and outpatients with grippe and mixed viral infections in various seasonal epidemic. In the
trial of remantadine 742 school children and 60 children at the age of 3 to 6 years with type A, B or A + B influenza, influenza
in association with other acute viral respiratory tract infections or acute viral respiratory tract infections of nongrippe etiology
were observed. 402 and 400 of them were given remantadine and placebo respectively. The drug was used in a single dose of 1.5 mg/kg
body weight 3 times a day for 3 days. In the trial of arbidole 158 children at the age of 1 to 14 years with type A influenza,
influenza + acute viral respiratory tract infection and acute viral respiratory tract infection of nongrippe etiology were observed.
The arbidole daily dose of 10 mg/kg body weight was given in 4 portions for 5 days. Both the drugs were shown to be therapeutically
efficient in all the grippe types and acute viral respiratory tract infections. The highest efficacy was observed when the use of
the drugs was started at the early stages. With the use of the drugs the periods of fever, other intoxication signs and virus isolation
decreased. No adverse reactions were recorded. The drugs had no inhibitory effect on the cellular and humoral immunity and on production
of antiviral antibodies. The dynamics of the indices of the cellular immunity and macrophages confirmed the arbidole immunostimulating action.
PMID: 9791684 [PubMed - indexed for MEDLINE]
Original Russian Document .pdf
Vestn Ross Akad Med Nauk. 1996;(8):34-7. - Full text not available at this time
Beliaev AL, Burtseva EI, Slepushkin AN, Beliaeva NA,
Nosik NN, Lavrukhina LA, Maksimova LN, Feklisova LV, Shibekova VM, Danina NF,
Tselipanova EE, Bylinkina SA, Voitsekhovskaia EM, Sominina AA.
The antiviral drug arbidol reduces influenza and
acute respiratory diseases (ARD) in children by 1.5-2 times when given in a
dose of 0.1-0.2 g 2-3 or 5 times a week, by making influenza and ARD milder
and decreasing their duration by 1.4-2.8 days. Unified regimens for prophylactic
use of arbidole in influenza and ARD in children and adults are proposed.
PMID: 8963194 [PubMed - indexed for MEDLINE]
Zh Mikrobiol Epidemiol Immunobiol. 1993 Sep-Oct;(5):40-3. - Full text not available at this time
The new chemical preparation arbidol: its prophylactic efficacy during influenza epidemics
Gagarinova VM, Ignat'eva GS, Sinitskaia LV, Ivanova AM, Rodina MA, Tur'eva AV.
n four controlled observations on the organized groups of students and industrial
workers during the epidemics of influenza A in 1988-1989 Arbidol, a new chemopreparation, was found to be
well tolerated and to produce a pronounced prophylactic effect when administered in a dose of 0.2 g (2 tablets
of 0.1 g) daily for 10-18 days. After the 18-day prophylactic course of Arbidol the induction of serum interferon was found.
PMID: 8067142 [PubMed - indexed for MEDLINE]
Vopr Virusol. 1991 Sep-Oct;36(5):380-1. - Full text not available at this time
The protective action of arbidol during a rise in respiratory diseases in 1990
Obrosova-Serova NP, Burtseva EI, Nevskii IM, Karmanova RI, Nazarov VI, Pitkenen AA,
Prophylactic properties of a new chemical drug, arbidol, against acute respiratory
diseases (ARD) were studied. Arbidol given daily in a dose of 0.2 g for 19 days reduced the morbidity rate
2.3-fold in adults during an outbreak of ARD. Geometric mean titres of antibodies to respiratory viruses
among healthy persons did not change after treatment with arbidol indicating the lack of immunosuppressive
properties in the drug. The prophylactic effect of arbidol may be due to both specific effect of the drug
on influenza and parainfluenza viruses, and its interferon-inducing and immunity-stimulating properties.
PMID: 1666474 [PubMed - indexed for MEDLINE]
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