Research progress of anti-influenza virus agents / 药学学报

Influenza is a major threat to millions of people worldwide. Vaccines and antiviral agents are two main options available to reduce the impact of the influenza virus, while anti-influenza agents are the most effective means to prevent the transmission of the highly contagious virus and to treat the epidemics of disease. At present, four anti-influenza agents have been approved by the FDA for the treatment of influenza, including two M2 protein ion channel inhibitors-amantadine and rimantadine and two neuraminidase inhibitors-zanamivir and oseltamivir. Arbidol hydrochloride, launched in Russia, is a potent inhibitor of influenza virus, too. Neuraminidase inhibitors could be classified generally by structure into six different kinds: sialic acid derivatives, benzoic acid derivatives, cyclohexene derivatives, cyclopentane derivatives, pyrrolidine derivatives and natural products. In this paper, recent progress in the research of the action mechanisms and structure-activity relationships of these anti-influenza virus agents were reviewed.

Flu channel drug resistance: a tale of two sites

The M2 proteins of influenza A and B virus, AM2 and BM2, respectively, are transmembrane proteins that oligomerize in the viral membrane to form proton-selective channels. Proton conductance of the M2 proteins is required for viral replication; it is believed to equilibrate pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation. In addition to the role of M2 in proton conductance, recent mutagenesis and structural studies suggest that the cytoplasmic domains of the M2 proteins also play a role in recruiting the matrix proteins to the cell surface during virus budding. As viral ion channels of minimalist architecture, the membrane-embedded channel domain of M2 has been a model system for investigating the mechanism of proton conduction. Moreover, as a proven drug target for the treatment of influenza A infection, M2 has been the subject of intense research for developing new anti-flu therapeutics. AM2 is the target of two anti-influenza A drugs, amantadine and rimantadine, both belonging to the adamantane class of compounds. However, resistance of influenza A to adamantane is now widespread due to mutations in the channel domain of AM2. This review summarizes the structure and function of both AM2 and BM2 channels, the mechanism of drug inhibition and drug resistance of AM2, as well as the development of new M2 inhibitors as potential anti-flu drugs.

[Emerging and pandemic of influenza A[H1N1]]

Influenza is one of the known viral infectious diseases, which has killed millions of peoples during pandemics, epidemics and sporadic forms. One of the most remarkable features of influenza virus is the frequency of changes in antigenicity. Alteration of the antigen structure of the virus leads to infection with variants to which little or no resistance is present in the population at risk. Pandemics of influenza type A, result from the emergence of a new virus which the population contains no or limited immunity to it. The interval between pandemics is 10-30 years. But Influenza virus has been causing epidemics of febrile respiratory disease every 1 to 3 years. Pandemic [H1N1] 2009 is a new virus that has not circulated among human population before. This virus is different from previous or current human seasonal influenza viruses. Influenza type A[H1N1] virus is transmitted by inhaling infected droplets expelled by coughing or sneezing or by touching contaminated hands or surfaces as the same as the normal seasonal flu. The symptoms and signs of A[H1N1] influenza are as similar as seasonal influenza and include fever, coughing, runny nose and sore throat. Some people have also reported, nausea, vomiting and diarrhea. People with existing cardiovascular disease, respiratory disease, diabetes and cancer are at higher risk of serious complications. Asthma and other respiratory disease are other underlying conditions associated with severe disease. Pregnant women are at higher risk for more severe disease and obesity may be another risk factor for severe disease. To prevent spread, people should cover their mouth and nose when coughing or sneezing, stay at home when they are unwell, clean their hands regularly, and avoid crowded areas if possible. The pandemic virus is currently susceptible to neuraminidase inhibitors; Oseltamivir and Zanamivir but resistant to Amantadine and Rimantadine. Ministry of health and medical education, Center for Infectious Diseases Management in Islamic Republic of Iran is ready for control and management of novel influenza A[H1N1]

Swine flu: an old virus with a new face

This review is describing the current world status of the recently identified swine origin influenza virus A [H1N1] outbreak with special focus on Jordan. This recent outbreak originated in Mexico and spread to more than 40 countries including USA and has been caused by a novel swine origin influenza virus A [H1N1]. This virus is thought to be a result of a genetic reassortment process that took place in pigs. This disease affects mostly young people with symptoms that are similar to those of seasonal influenza. Sustained human-to-human transmission has been documented and the virus is so far resistant to both amantadine and rimantadine but susceptible to oseltamivir and zanamivir. The World Health Organization [WHO] has raised the level of influenza pandemic to phase 5 and future speculations seem to be uncertain. Laboratory diagnosis is confirmed using a swine virus real-time, reverse transcriptase PCR test. No cases have been confirmed in Jordan. Nevertheless, Jordanian health authorities have started a very serious cascade of actions based on a comprehensive preparedness plan and supported by the already available infrastructure, increasing stockpiles of medications and protective equipments, and strengthening infection control preparedness of health care facilities

Prevention and Treatment of Influenza

Influenza is a disease known to continue to afflict a large number f people and cause many deaths throughout the world. Influenza A and B are the two types of influenza that cause epidemic human disease. The influenza illness is characterized by the abrupt onset of fever, myalgia, headache, and sore throat. Amantadine and rimantadine have been used to treatment and prophylaxis of influenza, but these agents can only reduce symptomatic illness due to influenza A virus and are ineffective against influenza B virus. Inhibitors of influenza neuraminidase constitute a new class of anti-influenza agents that reduce replication of influenza A and influenza B. Vaccination against influenza virus is the primary strategy to reduce the morbidity and mortality associated with influenza.

Influenza: una revisión de su quimioprofilaxis y terapéutica anti viral / Influenza: chemoprophylaxis and antiviral treatment

Diferentes agentes antivirales están disponibles para ser utilizados de manera profiláctica o terapéutica en las infecciones por el virus influenza. Los inhibidores de la neuraminidasa viral tienen la ventaja de actuar eficazmente sobre el virus A y B de la influenza, logrando un mejor espectro antiviral que la actividad restringida sobre el virus A presente en amantadina y rimantadina. El espectro antiviral de estas moléculas junto a la evidencia disponible en los diversos ensayos de eficacia clínica, respaldan el uso de estos fármacos para acortar la enfermedad y disminuir la severidad y complicaciones de la influenza. La eficacia de zanamivir y oseltamivir para este propósito es similar y ambas presentan reacciones adversas menores propias de la vía de administración nasal u oral que debe emplearse en cada caso. No obstante estas ventajas, el costo de estos medicamentos es elevado y limita su aplicación hacia el escenario terapéutico, especialmente en pacientes de alto riesgo. En situaciones donde la limitación económica es importante, amantadina en dosis apropiada, puede todavía ser considerada como una alternativa costo-efectiva para el manejo de los pacientes con influenza o para la intervención en grupos de riesgo no vacunados

Influenza en el año 2000 / Influenza at year 2000

Cada año, la influenza se asocia a una significativamortalidad y morbilidad especialmente entre los ancianos.La vacuna contra la influenza reduce los riesgos de enfermar. El éxito en la prevención de la mortalidad y morbilidad por influenza reside principalmente en la administración oportuna de la vacuna antiviral a los grupos de alto riesgo. En algunas situaciones puede estar indicado el uso de quimioprofilaxis antiviral con rimantadina o amantadina

Uso de la rimantadina en el tratamiento de la gripe / Use of rimantadine in the treatment of grippe

Se realizó diagnóstico rápido por inmunofluorescencia indirecta y aislamiento de una cepa del virus de influenza A(H3N2) entre enfermos y obreros del Instituto. Se aplicó tratamiento antigripal con rimantadina a un grupo de voluntarios, en las primeras 48 horas del inicio de la enfermedad para evaluar los resultados de uso curativo. Se administró la rimantadina, 1 tableta(50 mg) cada 8 horas durante 5 días. Se escogió otro grupo de enfermos como control , en éstos se utilizó un placebo. Ambos grupos se seleccionaron por el método de aleatorización por bloques realizando el estudio a doble ciega. Fueron tratados 18 pacientes, 10 del grupo estudio y 8 del control, en el primero se observó disminución de las manifestaciones clínicas a partir del segundo día de tratamiento y alto porcentaje de curación al tercero; no así en el grupo control en quienes todo fue más tardío. No se encontraron reacciones medicamentosas al tratamiento con rimantidina

Prevención y control de la influenza: breve revisión del tema / Prevention and control of influenza: brief review of the theme

Se expone una actualización de las diferentes formas de lucha contra la influenza o gripe, se destacan los tipos de vacunas y grupos que el Comité Asesor de las Prácticas de Inmunizaciones recomienda para su aplicación. Además, se señalan los medicamentos más frecuentemente utilizados contra el virus de influenza A, tales como la amantadina (1-adamantanamina HCL) y la rimantadina (alfa-metil-1-adamantanametilamina HCL) y se especifican sus usos terapéutico-curativo y quimioprofiláctico, además de sus reacciones secundarias. Se evidencia que el uso combinado de la inmunización junto con medicamentos antivirales es lo que ha demostrado ser altamente efectivo en la prevención y el control de tan importante problema de salud