神经氨酸酶抑制剂
一类抑制神经氨酸酶活性的抗病毒药物 / 維基百科,自由的 encyclopedia
神经氨酸酶抑制剂(neuraminidase inhibitors,NAIs)是一类抑制神经氨酸酶活性的抗病毒药物。其通过阻断流感病毒的神经氨酸酶,从而阻止病毒出芽,进而抑制病毒繁殖。神经氨酸酶抑制剂包括奥司他韦(达菲)(一种前药)、扎那米韦(乐感清)、拉尼米韦(Inavir)、帕拉米韦及一系列正在研发中的新药。与仅对甲型流感起作用的M2离子通道蛋白抑制剂不同,神经氨酸酶抑制剂对甲型流感和乙型流感均有效 [1] [2] [3][4]。
神经氨酸酶抑制剂奥司他韦和扎那米韦在美国和欧洲被批准用于治疗和预防流感。帕拉米韦通过结合并抑制流感病毒的神经氨酸酶活化而产生药理活性,其作用时间比奥司他韦和扎那米韦都要长。 [5]拉尼米韦从细胞中缓慢释放进入呼吸道,其抗流感病毒作用同样持久,但其维持持久作用的机理不同于帕拉米韦[6]。
近年来,神经氨酸酶抑制剂的疗效备受争议[7][8][9]。然而,在2009年H1N1流感大流行之后,许多国家和地区都宣称流感早期使用神经氨酸酶抑制剂治疗可有效减少严重病例和死亡率[10][11][12][13]。
统计报告显示,全国/地区范围内使用神经氨酸酶抑制剂治疗流感样疾病的国家和地区中,有症状感染者的死亡率很低,这是因为这些国家普遍在流感患者感染早期便使用神经氨酸酶抑制剂[14]。尽管这些国家和地区广泛使用奥司他韦,但尚未出现对奥司他韦具有耐药性的流感病毒引起的爆发,也没有出现对奥司他韦具有耐药性的流感病毒引起的严重疾病的报道[14]。美国疾病控制中心仍然建议并发症相关高危人群,老年人以及首次出现流感相关症状后48小时内的低危人群使用奥司他韦治疗流感[15]。
神经氨酸酶抑制剂常见的副作用为恶心和呕吐。已有报道称儿童服用奥司他韦后可出现行为异常,如谵妄和幻觉,这可能是流感相关症状的延伸[14]。这些副作用一般发生于流感早期,即流感病发后48小时内。因此,专家建议,无论患儿是否接受神经氨酸酶抑制剂治疗,父母都应密切监视流感病发后48小时内的患儿体征[14]。
常见神经氨酸酶抑制剂
- 奥司他韦 (达菲)
- 帕拉米韦 (Rapivab)
- 扎那米韦 (乐感清)
- 拉尼米韦
临床使用的神经氨酸酶抑制剂结构
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扎那米韦 | 奥司他韦 | 帕拉米韦 | 拉尼米韦 |
天然产物中的神经氨酸酶抑制剂
参考文献
- Smith, B. J.; McKimm-Breshkin, J. L.; McDonald, M.; Fernley, R. T.; Varghese, J. N.; Colman, P. M. Structural Studies of the Resistance of Influenza Virus Neuramindase to Inhibitors. Journal of Medicinal Chemistry. 2002, 45 (11): 2207–12. PMID 12014958. doi:10.1021/jm010528u.
- Gubareva, Larisa V. Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors. Virus Research. 2004, 103 (1–2): 199–203. PMID 15163510. doi:10.1016/j.virusres.2004.02.034.
- This flash animation shows the mode of action of oseltamivir (Tamiflu) 互联网档案馆的存檔,存档日期2005-10-23.. pharmasquare.org
- Replication of influenza virus (页面存档备份,存于互联网档案馆). mvm.ed.ac.uk
- Bantia, Shanta; Arnold, C. Shane; Parker, Cynthia D.; Upshaw, Ramanda; Chand, Pooran. Anti-influenza virus activity of peramivir in mice with single intramuscular injection. Antiviral Research. 1 January 2006, 69 (1): 39–45. ISSN 0166-3542. PMID 16325932. doi:10.1016/j.antiviral.2005.10.002.
- Ishizuka, Hitoshi; Yoshiba, Satoshi; Okabe, Hiromi; Yoshihara, Kazutaka. Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in healthy male volunteers. Journal of Clinical Pharmacology. 1 November 2010, 50 (11): 1319–1329. ISSN 1552-4604. PMID 20145259. doi:10.1177/0091270009356297.
- Jefferson, Tom; Jones, Mark; Doshi, Peter; Spencer, Elizabeth A.; Onakpoya, Igho; Heneghan, Carl J. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 9 April 2014, 348: g2545 [2021-01-15]. ISSN 1756-1833. PMC 3981975
. PMID 24811411. doi:10.1136/bmj.g2545. (原始内容存档于2019-10-31).
- Hsu, Jonathan; Santesso, Nancy; Mustafa, Reem; Brozek, Jan; Chen, Yao Long; Hopkins, Jessica P.; Cheung, Adrienne; Hovhannisyan, Gayane; Ivanova, Liudmila; Flottorp, Signe A.; Saeterdal, Ingvil; Wong, Arthur D.; Tian, Jinhui; Uyeki, Timothy M.; Akl, Elie A.; Alonso-Coello, Pablo; Smaill, Fiona; Schünemann, Holger J. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Annals of Internal Medicine. 3 April 2012, 156 (7): 512–524. ISSN 1539-3704. PMC 6679687
. PMID 22371849. doi:10.7326/0003-4819-156-7-201204030-00411.
- Heneghan, Carl J.; Onakpoya, Igho; Thompson, Matthew; Spencer, Elizabeth A.; Jones, Mark; Jefferson, Tom. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 9 April 2014, 348: g2547 [2021-01-15]. ISSN 1756-1833. PMC 3981976
. PMID 24811412. doi:10.1136/bmj.g2547. (原始内容存档于2021-03-23).
- Louie, Janice K.; Acosta, Meileen; Jamieson, Denise J.; Honein, Margaret A. Severe 2009 H1N1 Influenza in Pregnant and Postpartum Women in California. New England Journal of Medicine. 2010, 362 (1): 27–35. PMID 20032319. doi:10.1056/nejmoa0910444.
- Jain, Seema; Kamimoto, Laurie; Bramley, Anna M.; Schmitz, Ann M.; Benoit, Stephen R.; Louie, Janice; Sugerman, David E.; Druckenmiller, Jean K.; Ritger, Kathleen A.; Chugh, Rashmi; Jasuja, Supriya; Deutscher, Meredith; Chen, Sanny; Walker, John D.; Duchin, Jeffrey S.; Lett, Susan; Soliva, Susan; Wells, Eden V.; Swerdlow, David; Uyeki, Timothy M.; Fiore, Anthony E.; Olsen, Sonja J.; Fry, Alicia M.; Bridges, Carolyn B.; Finelli, Lyn. Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009. New England Journal of Medicine. 12 November 2009, 361 (20): 1935–1944. CiteSeerX 10.1.1.183.7888
. ISSN 0028-4793. PMID 19815859. doi:10.1056/NEJMoa0906695.
- Domínguez-Cherit, Guillermo; Lapinsky, Stephen E.; Macias, Alejandro E.; Pinto, Ruxandra; Espinosa-Perez, Lourdes; de la Torre, Alethse; Poblano-Morales, Manuel; Baltazar-Torres, Jose A.; Bautista, Edgar; Martinez, Abril; Martinez, Marco A.; Rivero, Eduardo; Valdez, Rafael; Ruiz-Palacios, Guillermo; Hernández, Martín; Stewart, Thomas E.; Fowler, Robert A. Critically Ill patients with 2009 influenza A(H1N1) in Mexico. JAMA. 4 November 2009, 302 (17): 1880–1887. ISSN 1538-3598. PMID 19822626. doi:10.1001/jama.2009.1536
.
- Zarychanski, R.; Stuart, T. L.; Kumar, A.; Doucette, S.; Elliott, L.; Kettner, J.; Plummer, F. Correlates of severe disease in patients with 2009 pandemic influenza (H1N1) virus infection. Canadian Medical Association Journal. 2010, 182 (3): 257–264. ISSN 0820-3946. PMC 2826467
. PMID 20093297. doi:10.1503/cmaj.091884.
- Sugaya, Norio. Widespread use of neuraminidase inhibitors in Japan. Journal of Infection and Chemotherapy. 1 October 2011, 17 (5): 595–601. ISSN 1437-7780. PMID 21850418. doi:10.1007/s10156-011-0288-0.
- CDC Online Newsroom - "Have You Heard?" Archive: 2014 - Influenza A Variant Virus. cdc.gov. [2021-01-15]. (原始内容存档于2017-01-18).
- Swaminathan K, Dyason JC, Maggioni A, von Itzstein M, Downard KM. Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry. Anal Bioanal Chem. 2013, 405 (20): 6563–72. PMID 23748498. doi:10.1007/s00216-013-7068-x.
- Kim, Jang Hoon; Ryu, Young Bae; Lee, Woo Song; Kim, Young Ho. Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from Corydalis turtschaninovii rhizome. Bioorganic & Medicinal Chemistry. 2014-11-01, 22 (21): 6047–6052. ISSN 1464-3391. PMID 25277281. doi:10.1016/j.bmc.2014.09.004
.