Biochem Biophys Res Commun. Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus.

[Giuseppe]

Biochem Biophys Res Commun. 2009 Aug 28;386(3):432-6. Epub 2009 Jun 10.

Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus.

Wang SQ, Du QS, Huang RB, Zhang DW, Chou KC. - College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.


The neuraminidase (NA) of influenza virus is the target of anti-flu drugs oseltamivir and zanamivir. Clinical practices showed that oseltamivir was effective to treat the 2009-H1N1 influenza but failed to the 2006-H5N1 avian influenza. To perform an in-depth analysis on such a drug-resistance problem, the 2009-H1N1-NA structure was developed. To compare it with the crystal 2006-H5N1-NA structure as well as the 1918 influenza virus H1N1-NA structure, the multiple sequential and structural alignments were performed. It has been revealed that the hydrophobic residue Try347 in H5N1-NA does not match with the hydrophilic carboxyl group of oseltamivir as in the case of H1N1-NA. This may be the reason why H5N1 avian influenza virus is drug-resistant to oseltamivir. The finding provides useful insights for how to modify the existing drugs, such as oseltamivir and zanamivir, making them not only become more effective against H1N1 virus but also effective against H5N1 virus.

PMID: 19523442 [PubMed - indexed for MEDLINE]
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[gsgs]

Re: Biochem Biophys Res Commun. Insights from investigating the interaction of oseltamivir (Tamiflu) with neuraminidase of the 2009 H1N1 swine flu virus.

try347

try = Y

347 with the 20-deletion = 327 ?

can't find the Y

also, I had thought that Tamiflu _did_ work in H5N1 ?!?

>Index Qinghai
001   MNPNQKIITI GSICMVIGIV SLMLQIGNMI SIWVSHSIQT GNQRQAEPIS 
051                         NTKFLTEKAV ASVTLAGNSS LCPISGWAVY
101   SKDNSIRIGS RGDVFVIREP FISCSHLECR TFFLTQGALL NDKHSNGTVK
151   DRSPHRTLMS CPVGEAPSPY NSRFESVAWS ASACHDGTSW LTIGISGPDN
201   GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT VMTDGPSNGQ
251   ASYKIFKMEK GKVVKSVELD APNYHYEECS CYPDAGEITC VCRDNWHGSN
301   RPWVSFNQNL EYQIGYICSG VFGDNPRPND GTGSCGPVSP NGAYGVKGFS
351   FKYGNGVWIG RTKSTNSRSG FEMIWDPNGW TGTDSSFSVK QDIVAITDWS
401   GYSGSFVQHP ELTGLDCIRP CFWVELIRGR PKESTIWTSG SSISFCGVNS
451   DTVSWSWPDG AELPFTIDK}

>A/Brevig Mission/1/1918(H1N1)
001   MNPNQKIITI GSICMVVGII SLILQIGNII SIWVSHSIQT GNQNHPETCN
051   QSIITYENNT WVNQTYVNIS NTNVVAGQDA TSVILTGNSS LCPISGWAIY
101   SKDNGIRIGS KGDVFVIREP FISCSHLECR TFFLTQGALL NDKHSNGTVK
151   DRSPYRTLMS CPVGEAPSPY NSRFESVAWS ASACHDGMGW LTIGISGPDN
201   GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT IMTDGPSNGQ
251   ASYKILKIEK GKVTKSIELN APNYHYEECS CYPDTGKVMC VCRDNWHGSN
301   RPWVSFDQNL DYQIGYICSG VFGDNPRPND GTGSCGPVSS NGANGIKGFS
351   FRYDNGVWIG RTKSTSSRSG FEMIWDPNGW TETDSSFSVR QDIVAITDWS
401   GYSGSFVQHP ELTGLDCMRP CFWVELIRGQ PKENTIWTSG SSISFCGVNS
451   DTVGWSWPDG AELPFSIDK}