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Pathway Description
Oseltamivir Action Pathway
Homo sapiens
Drug Action Pathway
Oseltamivir is a pro-drug neuraminidase inhibitor used in the prophylaxis and treatment of influenza A (including pandemic H1N1) and B. Oseltamivir is extensively converted to the active metabolite oseltamivir caboxylate, by liver esterases. Viral neuraminidase enzymes are glycoproteins found on the virion surface which are important in the viral release from infected cells in order to further spread the virus in the body. Viral Neuraminidase helps viruses to be released from the plasma membrane of the host cell after budding by cleaving terminal sialic acid resides from glycan structures on the surface of the infected cell. It is also important in viral entry into uninfected cells. Both the inhibition of entry and release reduces viral shedding and infectivity.
References
Oseltamivir Pathway References
McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M: Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother. 2003 Jul;47(7):2264-72. doi: 10.1128/AAC.47.7.2264-2272.2003.
Pubmed: 12821478
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. doi: 10.1038/nrd2132.
Pubmed: 17016423
Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. doi: 10.1038/nrd2199.
Pubmed: 17139284
Ward P, Small I, Smith J, Suter P, Dutkowski R: Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005 Feb;55 Suppl 1:i5-i21. doi: 10.1093/jac/dki018.
Pubmed: 15709056
Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG: Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. BMJ. 2003 Jun 7;326(7401):1235. doi: 10.1136/bmj.326.7401.1235.
Pubmed: 12791735
Oseltamivir FDA Label: https://s3-us-west-2.amazonaws.com/drugbank/cite_this/attachments/files/000/003/094/original/209113Orig1s000lbl.pdf?1548284241
Oseltamivir EMA Label: https://s3-us-west-2.amazonaws.com/drugbank/cite_this/attachments/files/000/003/097/original/tamiflu-epar-product-information_en.pdf?1548284404
Oseltamivir New Zealand Product Information: https://s3-us-west-2.amazonaws.com/drugbank/cite_this/attachments/files/000/003/115/original/Tamiflucapsusp.pdf?1548355321
McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M: Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Antimicrob Agents Chemother. 2003 Jul;47(7):2264-72. doi: 10.1128/AAC.47.7.2264-2272.2003.
Pubmed: 12821478
Du QS, Wang SQ, Chou KC: Analogue inhibitors by modifying oseltamivir based on the crystal neuraminidase structure for treating drug-resistant H5N1 virus. Biochem Biophys Res Commun. 2007 Oct 19;362(2):525-31. doi: 10.1016/j.bbrc.2007.08.025. Epub 2007 Aug 13.
Pubmed: 17707775
Wang MZ, Tai CY, Mendel DB: Mechanism by which mutations at his274 alter sensitivity of influenza a virus n1 neuraminidase to oseltamivir carboxylate and zanamivir. Antimicrob Agents Chemother. 2002 Dec;46(12):3809-16. doi: 10.1128/AAC.46.12.3809-3816.2002.
Pubmed: 12435681
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
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