{"title":"当前和未来的抗流感病毒药物","authors":"N. Uchide, K. Ohyama, H. Toyoda","doi":"10.2174/1876518101002010034","DOIUrl":null,"url":null,"abstract":"In 2009, we have been experiencing a new pandemic of novel influenza virus type A (H1N1) infection. The human beings still face the threat of highly pathogenic avian influenza A (H5N1) virus. Many patients with influenza virus infection have died due to severe complications even though receiving intensive care. This suggests the need for new treatment strategies of severe influenza-associated complications. In cases of severe influenza-associated complications, pathological manifestations are as a result of complex biological consequences, such as apoptosis induction, macrophage activation, oxidative damage and increased production of pro-inflammatory cytokines. Recent studies have revealed that the pathogenesis of severe influenza-associated complications involves not only the virus replication-mediated apoptotic cell death in the infected cells but also non-infected cell injury by toxicity of reactive oxygen species derived from macro- phages phagocytosing apoptotic cells, and that pro-inflammatory cytokines produced by the virus-infected host cells play a critical role in the activation of macrophages. These findings provide a possibility that an agent with antiviral and antioxidant activities can be a drug of choice for the treatment of patients with severe influenza-associated complications. Selected antioxidants, such as pyrrolidine dithiocarbamate, N-acetyl-L-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin and certain types of flavonoids, possess both activities. The combination of antioxidants, such as superoxide dismutase and N-acetyl-L-cysteine, with antiviral drug ribavirin synergistically reduced the lethal effect of influenza virus infection. Accumulating a number of evidence highlights a potential of selected antioxidants for treatment of severe influenza-associated complications and a possibility that combination of antioxidants with current anti-influenza drugs can improve conventional influenza chemotherapy.","PeriodicalId":22920,"journal":{"name":"The Open Antimicrobial Agents Journal","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2010-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"8","resultStr":"{\"title\":\"Current and Future Anti-Influenza Virus Drugs\",\"authors\":\"N. Uchide, K. Ohyama, H. Toyoda\",\"doi\":\"10.2174/1876518101002010034\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"In 2009, we have been experiencing a new pandemic of novel influenza virus type A (H1N1) infection. The human beings still face the threat of highly pathogenic avian influenza A (H5N1) virus. Many patients with influenza virus infection have died due to severe complications even though receiving intensive care. This suggests the need for new treatment strategies of severe influenza-associated complications. In cases of severe influenza-associated complications, pathological manifestations are as a result of complex biological consequences, such as apoptosis induction, macrophage activation, oxidative damage and increased production of pro-inflammatory cytokines. Recent studies have revealed that the pathogenesis of severe influenza-associated complications involves not only the virus replication-mediated apoptotic cell death in the infected cells but also non-infected cell injury by toxicity of reactive oxygen species derived from macro- phages phagocytosing apoptotic cells, and that pro-inflammatory cytokines produced by the virus-infected host cells play a critical role in the activation of macrophages. These findings provide a possibility that an agent with antiviral and antioxidant activities can be a drug of choice for the treatment of patients with severe influenza-associated complications. Selected antioxidants, such as pyrrolidine dithiocarbamate, N-acetyl-L-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin and certain types of flavonoids, possess both activities. The combination of antioxidants, such as superoxide dismutase and N-acetyl-L-cysteine, with antiviral drug ribavirin synergistically reduced the lethal effect of influenza virus infection. Accumulating a number of evidence highlights a potential of selected antioxidants for treatment of severe influenza-associated complications and a possibility that combination of antioxidants with current anti-influenza drugs can improve conventional influenza chemotherapy.\",\"PeriodicalId\":22920,\"journal\":{\"name\":\"The Open Antimicrobial Agents Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2010-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"8\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Open Antimicrobial Agents Journal\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/1876518101002010034\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Open Antimicrobial Agents Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1876518101002010034","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
In 2009, we have been experiencing a new pandemic of novel influenza virus type A (H1N1) infection. The human beings still face the threat of highly pathogenic avian influenza A (H5N1) virus. Many patients with influenza virus infection have died due to severe complications even though receiving intensive care. This suggests the need for new treatment strategies of severe influenza-associated complications. In cases of severe influenza-associated complications, pathological manifestations are as a result of complex biological consequences, such as apoptosis induction, macrophage activation, oxidative damage and increased production of pro-inflammatory cytokines. Recent studies have revealed that the pathogenesis of severe influenza-associated complications involves not only the virus replication-mediated apoptotic cell death in the infected cells but also non-infected cell injury by toxicity of reactive oxygen species derived from macro- phages phagocytosing apoptotic cells, and that pro-inflammatory cytokines produced by the virus-infected host cells play a critical role in the activation of macrophages. These findings provide a possibility that an agent with antiviral and antioxidant activities can be a drug of choice for the treatment of patients with severe influenza-associated complications. Selected antioxidants, such as pyrrolidine dithiocarbamate, N-acetyl-L-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin and certain types of flavonoids, possess both activities. The combination of antioxidants, such as superoxide dismutase and N-acetyl-L-cysteine, with antiviral drug ribavirin synergistically reduced the lethal effect of influenza virus infection. Accumulating a number of evidence highlights a potential of selected antioxidants for treatment of severe influenza-associated complications and a possibility that combination of antioxidants with current anti-influenza drugs can improve conventional influenza chemotherapy.