Relenza® publications

The following publications detail the work involved in the development of CSIRO’s Relenza®.

Patents

von Itzstein LM, Wu W-Y, Phan TV, Danylec B, Jin B, Colman PM, Varghese JN, 1997, ‘Derivatives and analogues of 2-deoxy-2,3-didehydro-N-acetyl neuraminic acid and their use as anti-viral agents’, U.S. Patent Number 5,648,379 U.S. – published by the inventors : von Itzstein LM, Wu W-Y, Phan TV, Danylec B, Jin B, on the same title respectively in 1994 and 1991 under the U.S. Patent Number 5,360,817 and the Publication Number WO/1991/016320.

Key publications

Colman PM, 2006, ‘Anti-influenza drugs from neuraminidase inhibitors’, In: Structure Based Drug Discovery – An Overview, Hubbard RE (ed), Royal Society of Chemistry, Cambridge, UK, pp.193-212.

Colman PM, 2005, ‘Zanamivir: an influenza virus neuraminidase inhibitor’, Expert Review of Anti-Infective Therapy, 3: 191-199.

Varghese JN, Smith PW, Sollis SL, Blick TJ, Sahasrabudhe A, McKimm-Breschkin JL, Colman PM, 1998, ‘Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase’, Structure, 6: 735-746.

von Itzstein M, Wu W-Y, Kok GB, Pegg MS, Dyason JC, Jin B, Phan TV, Smythe ML, White HF, Oliver SW, Colman PM, Varghese JN, Ryan DM, Woods JM, Bethel RC, Hotham VJ, Cameron JM, Penn CR, 1993, ‘Rational design of potent sialidase-based inhibitors of influenza virus replication’, Nature, 363: 418-423.

Varghese JN, McKimm-Breschkin J, Caldwell JB, Kortt AA, Colman PM, 1992, ‘The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor’, Proteins: Structure, Function, and Genetics, 14: 327-332.

Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, Air GM, Webster RG, 1987, ‘The three dimensional structure of a complex of antibody with influenza virus neuraminidase’, Nature, 326: 358-363.

Colman PM, Ward CW, 1985, ‘Structure and diversity of influenza virus neuraminidase’, Current Topics in Microbiology and Immunology, 114: 177-255.

Colman PM, Varghese JN, Laver WG, 1983, ‘Structure of the catalytic and antigenic sites in influenza virus neuraminidase’, Nature, 303: 41-44.

Varghese JN, Laver WG, Colman PM., 1983, ‘Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 Å resolution’, Nature, 303: 35-40.

Reviews

Epa VC, Colman PM, 2001, ‘Shape and electrostatic complementarity at viral antigen-antibody complexes’, In: Current Topics in Microbiology and Immunology, Burton DR (ed), Springer, 260: 45-53.

Woodhead M, Lavanchy D, Johnston S, Colman P, Fleming D, 2000, ‘Neuraminidase inhibitors: Progress in the management of influenza’, International Journal of Clinical Practice, 54: 604-610.

Colman PM, 1998, ‘Structure and function of the neuraminidase’, In: Textbook of Influenza, Nicholson KG, Webster RG, Hay AJ (eds), Blackwell Science, UK, Chapter 6: 65-73.

Colman PM, 1997, ‘Virus versus antibody’, Structure, 5: 591-593.

Colman PM, 1996, ‘The antigen-antibody complex: Structure and recognition’, In: Immunobiology, Bittar EE, Bittar N (eds), Principles of Medical Biology, JAI Press, Greenwich, Conn, 6: 107-120.

von Itzstein M, Colman PM, 1996, ‘Design and synthesis of carbohydrate-based inhibitors of protein-carbohydrate interactions’, Current Opinion in Structural Biology, 6: 703-709.

Colman PM, 1994, ‘Influenza virus neuraminidase: structure, antibodies, and inhibitors’, Protein Science, 3: 1687-1696.

Colman PM, 1994, ‘Structure-based drug design’, Current Opinion in Structural Biology, 4: 868-874.

Colman PM, 1994, ‘Effects of amino acid sequence changes on antibody-antigen interactions. A structural view of immune recognition by antibodies’, Research in Immunology, 145: 33-36.

Colman PM, 1991, ‘Antigen-antigen receptor interactions’, Current Opinion in Structural Biology, 1: 232-236.

Varghese JN, Tulip WR, Colman PM, 1990, ‘Influenza and antibody binding’, Today’s Life Science, 2: 12-19.

Colman PM, 1989, ‘Neuraminidase: Enzyme and antigen’, In: The Influenza Viruses, Krug RM (ed), Plenum, New York, Chapter 4: 175-218.

Colman PM, 1988, ‘Structure of antibody-antigen complexes: implications for immune recognition’, Advances in Immunology, 43: 99-132.

Colman PM, Air GM, Webster RG, Varghese JN, Baker AT, Lentz MR, Tulloch PA, Laver WG, 1987, ‘How antibodies recognize virus proteins’, Immunology Today, 8: 323-326.

Colman PM, 1984, ‘Structure and function of neuraminidase’, Peptide and Protein Reviews, 4: 215-255.

Laver WG, Colman PM, Ward CW, Varghese JM, Air GM, Webster RG, Hinshaw V, Brown L, Jackson D, 1984, ‘Influenza virus neuraminidase: structure and variation’, In: Molecular Virology and Epidemiology of Influenza, Stuart-Harris C, Potter CW (eds), Academic Press, pp.77-99.

Laver WG, Colman PM, Ward CW, Varghese JM, Air GM, Webster RG, 1984, ‘Influenza virus neuraminidase: structure and variation’, In: Segmented Negative Strand Viruses, Compans RW (ed), Academic Press, NY, pp.225-232.

Azad AA, Elleman TC, Laver WG, Ward CW, 1983, ‘Sequence changes associated with antigenic shift and drift in influenza virus neuraminidase’, In: Origin of Pandemic Influenza Virus, Laver WG (ed), Elsevier, New York, pp.59-76.

Original papers

McKimm-Breschkin JL, Selleck PW, Usman TB, Johnson MA, 2007, ‘Reduced sensitivity of influenza A (H5N1) to oseltamivir’, Emerging Infections Diseases, 13: 1354-1357.

Moscona A, McKimm-Breschkin J, 2007, ‘News about influenza B drug resistance that cannot be ignored’, Journal of the American Medical Association, 297: 1492-1493.

Hurt AC, Iannello P, Jachno K, Komadina N, Hampson AW, Barr IG, McKimm-Breschkin JL, 2006, ‘Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient’, Antimicrobial Agents and Chemotherapy, 50: 1872-1874.

Monto AS, McKimm-Breschkin JL, Macken C, Hampson AW, Hay A, Klimov A, Tashiro M, Webster RG, Aymard M, Hayden FG, Zambon M, 2006, ‘Detection of influenza viruses resistant to neuraminidase inhibitors in global surveillance during the first 3 years of their use’, Antimicrobial Agents and Chemotherapy, 50: 2395-2402.

Smith BJ, Huyton T, Joosten RP, McKimm-Breschkin JL, Zhang JG, Luo CS, Lou MZ, Labrou NE, Garrett TP, 2006, ‘Structure of a calcium-deficient form of influenza virus neuraminidase: implications for substrate binding’, Acta Crystallographica Section D Biological Crystallography, 62: 947-952.

Zurcher T, Yates PJ, Daly J, Sahasrabudhe A, Walters M, Dash L, Tisdale M, McKimm-Breschkin JL, 2006, ‘Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro‘, Journal of Antimicrobial Chemotherapy, 58: 723-732.

Hayden F, Klimov A, Tashiro M, Hay A, Monto A, McKimm-Breschkin J, Macken C, Hampson A, Webster RG, Amyard M, Zambon M, 2005, ‘Neuraminidase inhibitor susceptibility network position statement: antiviral resistance in influenza A/H5N1 viruses’, Antiviral Therapy, 10: 873-877.

McKimm-Breschkin JL, 2005, ‘Management of influenza virus infections with neuraminidase inhibitors: detection, incidence, and implications of drug resistance’, Treatments in Respiratory Medicine, 4: 107-116.

Macdonald SJ, Cameron R, Demaine DA, Fenton RJ, Foster G, Gower D, Hamblin JN, Hamilton S, Hart GJ, Hill AP, Inglis GG, Jin B, Jones HT, McConnell DB, McKimm-Breschkin J, Mills G, Nguyen V, Owens IJ, Parry N, Shanahan SE, Smith D, Watson KG, Wu WY, Tucker SP, 2005, ‘Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza’, Journal of Medicinal Chemistry, 48: 2964-2971.

Hurt AC, McKimm-Breschkin JL, McDonald M, Barr IG, Komadina N, Hampson AW, 2004, ‘Identification of a human influenza type B strain with reduced sensitivity to neuraminidase inhibitor drugs’, Virus Research, 103: 205-211.

Lawrence MC, Borg NA, Streltsov VA, Pilling PA, Epa VC, Varghese JN, McKimm-Breschkin JL, Colman PM, 2004, ‘Structure of the Haemagglutinin-neuraminidase from Human Parainfluenza Virus Type III’, Journal of Molecular Biology, 335: 1343-1357.

McKimm-Breschkin JL, Colman PM, Jin B, Krippner GY, McDonald M, Reece PA, Tucker SP, Waddington L, Watson KG, Wu W-Y, 2003, ‘Tethered neuraminidase inhibitors that bind an influenza virus: A first step towards a diagnostic method for influenza’, Angewandte Chemie International Edition, 42: 3118-3121.

McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M, 2003, ‘Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir’, Antimicrobial Agents and Chemotherapy, 47: 2264-2272.

Wetherall NT, Trivedi T, Zeller J, Hodges-Savola C, McKimm-Breschkin JL, Zambon M, Hayden FG, 2003, ‘Evaluation of neuraminidase enzyme assays using different substrates to measure susceptibility of influenza virus clinical isolates to neuraminidase inhibitors: report of the neuraminidase inhibitor susceptibility network’, Journal of Clinical Microbiology, 41: 742-750.

McKimm-Breschkin JL, 2002, ‘Neuraminidase inhibitors for the treatment and prevention of influenza’, Expert Opinion on Pharmacotherapy, 3: 103-112.

Smith BJ, McKimm-Breschkin JL, McDonald M, Fernley RT, Varghese JN, Colman PM, 2002, ‘Structural studies of the resistance of influenza virus neuraminidase to inhibitors’, Journal of Medicinal Chemistry, 45: 2207-2212.

Smith BJ, Colman PM, von Itzstein M, Danylec M, Varghese JN, 2001, ‘Analysis of inhibitor binding in influenza virus neuraminidase’, Protein Science, 10: 689-696.

McKimm-Breschkin JL, 2000, ‘Resistance of influenza viruses to neuraminidase inhibitors – a review’, Antiviral Research, 47: 1-17.

Blick TJ, Sahasrabudhe A, McDonald M, Owens IJ, Morley PJ, Fenton RJ, McKimm-Breschkin JL, 1998, ‘The interaction of neuraminidase and hemagglutinin mutations in influenza virus in resistance to 4-guanidino-Neu5Ac2en’, Virology, 246: 95-103.

Malby RL, McCoy AJ, Kortt AA, Hudson PJ, Colman PM, 1998, ‘Three-dimensional structures of single-chain Fv-neuraminidase complexes’, Journal of Molecular Biology, 279: 901-910.

McKimm-Breschkin JL, Sahasrabudhe A, Blick AJ, McDonald M, Colman PM, Hart GJ, Bethell RC, Varghese JN, 1998, ‘Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors’, Journal of Virology, 72: 2456-2462.

Sahasrabudhe A, Lawrence L, Epa VC, Varghese JN, Colman PM, McKimm-Breschkin JL, 1998, ‘Substrate, inhibitor, or antibody stabilizes the Glu 119 Gly mutant influenza virus neuraminidase’, Virology, 247: 14-21.

Taylor NR, Cleasby A, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethell R, Colman P, Varghese J, 1998, ‘Dihydropyrancarboxamides related to Zanamivir: A new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus Types A and B’, Journal of Medicinal Chemistry, 41:798-807.

Sahasrabudhe A, Ekkel S, Hampson AW, McKimm-Breschkin JL, 1997, ‘Use of oligonucleotide probes for selecting potential high-yielding influenza reassortants’, Journal of Virological Methods, 68: 139-145.

Varghese JN, Colman PM, van Donkelaar A, Blick TJ, Sahasrabudhe A, McKimm-Breschkin JL, 1997, ‘Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases’, Proc. of the National Academy of Science USA, *94, 11808-11812.

McKimm-Breschkin JL, Blick TJ, Sahasrabudhe A, Tiong T, Marshall D, Hart GJ, Bethell RC, Penn CR, 1996, ‘Generation and characterization of variants of NWS/G70C influenza virus after in vitro passage in 4-amino-Neu5Ac2en and 4-guanidino-Neu5Ac2en’, Antimicrobial Agents and Chemotherapy, 40: 40-46.

McKimm-Breschkin JL, McDonald M, Blick TJ, Colman PM, 1996, ‘Mutation in the Influenza Virus Neuraminidase Gene Resulting in Decreased Sensitivity to the Neuraminidase Inhibitor 4-Guanidino-Neu5Ac2en leads to Instability of the Enzyme’, Virology, 225: 240-242.

Smith PW, Sollis SL, Howes PD, Cherry PC, Cobley KN, Taylor H, Whittington AR, Scicinski J, Bethell RC, Taylor N, Skarzynski T, Cleasby A, Singh O, Wonacott A, Varghese J, Colman P, 1996, ‘Novel inhibitors of influenza sialidases related to GG167. Structure-activity, crystallographic and molecular dynamics studies with 4H-Pyran-2-carboxylic acid 6-carboxamides’, Bioorganic & Medicinal Chemistry Letters, 6: 2931-2936.

Blick TJ, Tiong T, Sahasrabudhe A, Varghese JN, Colman PM, Hart GH, Bethell RC, McKimm-Breschkin JL, 1995, ‘Generation and characterization of an influenza virus neuraminidase variant with decreased sensitivity to the neuraminidase-specific inhibitor 4-Guanidino-Neu5Ac2en’, Virology, 214: 475-484.

Varghese JN, Epa VC, Colman PM, 1995, ‘Three-dimensional structure of the complex of 4-guanidino-Neu5Ac2en and influenza virus neuraminidase’, Protein Science, 4: 1081-1087.

Gruen LC, McKimm-Breschkin JL, Caldwell JB, Nice EC, 1994, ‘Affinity ranking of influenza neuraminidase mutants with monoclonal antibodies using an optical biosensor, comparison with ELISA and slot blot assays’, Journal of Immunological Methods, 168: 91-100.

Kortt AA, Malby RL, Caldwell JB, Gruen LC, Ivancic N, Lawrence MC, Howlett GJ, Webster RG, Hudson PJ, Colman PM, 1994, ‘Recombinant anti-sialidase single-chain variable fragment antibody. Characterization, formation of dimer and higher-molecular-mass multimers and the solution of the crystal structure of the single-chain variable fragment/sialidase complex’, European Journal of Biochemistry, 221: 151-157.

Malby RL, Tulip WR, Harley VR, McKimm-Breschkin JL, Laver WG, Webster RG, Colman PM, 1994, ‘The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody’, Structure, 2: 733-746.

Colman PM, Hoyne PA, Lawrence MC, 1993, ‘Sequence and structure alignment of paramyxovirus haemagglutinin-neuraminidase (HN) with influenza virus neuraminidase’, Journal of Virology, 67: 2972-2980.

Malby RL, Caldwell JB, Gruen LC, Harley VR, Ivancic N, Kortt AA, Lilley GG, Power BE, Webster RG, Colman PM, Hudson PJ, 1993, ‘Recombinant anti-neuraminidase single chain antibody: expression, characterization, and crystallization in complex with antigen’, Proteins: Structure, Function, and Genetics, 16: 57-63.

Mather KA, White JF, Hudson PJ, McKimm-Breschkin JL, 1992, ‘Expression of influenza neuraminidase in baculovirus-infected cells’, Virus Research, 26: 127-139.

Tulip WR, Varghese JN, Webster RG, Laver WG, Colman PM, 1992, ‘Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface’, Journal of Molecular Biology, 227: 149-159.

Tulip WR, Varghese JN, Laver WG, Webster RG, Colman PM, 1992, ‘Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex’, Journal of Molecular Biology, 227: 122-148.

McKimm-Breschkin JL, Caldwell JB, Guthrie RE, Kortt AA, 1991, ‘A new method for the purification of the influenza A virus neuraminidase’, Journal of Virological Methods, 32: 121-124.

Tulip WR, Varghese JN, Baker AT, van Donkelaar A, Laver WG, Webster RG, Colman PM, 1991, ‘Refined atomic structures of N9 subtype influenza virus neuraminidase and escape mutants’, Journal of Molecular Biology, 221: 487-497.

Varghese JN, Colman PM, 1991, ‘Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 Å resolution’, Journal of Molecular Biology, 221: 473-486.

Colman PM, Tulip WR, Varghese JN, Tulloch PA, Baker AT, Laver WG, Air GM, Webster RG, 1989, ‘Three-dimensional structures of influenza virus neuraminidase-antibody complexes’, Philosophical Transactions of the Royal Society, London, B323: 511-518.

Harley VR, Ward CW, Hudson PJ, 1989, ‘Molecular cloning and analysis of the N5 neuraminidase sub-type from an avian influenza virus’, Virology, 169: 239-243.

Varghese JN, Webster RG, Laver WG, Colman PM, 1988, ‘The structure of an escape mutant of the glycoprotein N2 neuraminidase of Influenza Virus A/Tokyo/3/67 at 3 Å’, Journal of Molecular Biology, 200: 201-203.

Air GM, Webster RG, Colman PM, Laver WG, 1987, ‘Distribution of sequence differences in influenza N9 neuraminidase of tern and whale viruses, and crystallisation of the whale neuraminidase complexed with antibodies’, Virology, 160: 346-354.

Baker AT, Varghese JN, Laver WG, Air GM, Colman PM, 1987, ‘The three dimensional structure of neuraminidase of subtype N9 from an avian influenza virus’, Proteins: Structure, Function and Genetics, 2: 111-117.

Webster RG, Air GM, Metzger DW, Colman PM, Varghese JN, Baker AT, Laver WG, 1987, ‘Antigenic structure and variation in an influenza N9 neuraminidase’, Journal of Virology, 61: 2910-2916.

Laver WG, Webster RG, Colman PM, 1986, ‘Crystals of antibodies complexed with influenza virus neuraminidase show isosteric binding of antibody to wild-type and variant antigens’, Virology, 156: 181-184.

Tulloch PA, Colman PM, Davis PC, Laver WG, Webster RG, Air GM, 1986, ‘Electron and X-ray diffraction studies of influenza neuraminidase complexed with monoclonal antibodies’, Journal of Molecular Biology, 190: 215-225.

Air GM, Ritchie LR, Laver WG, Colman PM, 1985, ‘Gene and protein sequence of an influenza neuraminidase with haemagglutinin activity’, Virology, 145: 117-122.

Laver WG, Colman PM, Webster RG, Hinshaw V, Air GM, 1984, ‘Influenza virus neuraminidase with haemagglutinin activity’, Virology, 137: 314-323.

Ward CW, Colman PM, Laver WG, 1983, ‘The disulphide bonds of an Asian influenza virus neuraminidase’, FEBS Letters, 153: 29-33.

Ward CW, Murray JM, Roxburgh CM, Jackson DC, 1983, ‘Chemical and antigenic characterization of the carbohydrate side chains of an Asian (N2) influenza virus neuraminidase’, Virology, 126: 370-375.

Blok J, Air GM, Laver WG, Ward CW, Lilley GG, Woods EF, Roxburgh CM, Inglis AS, 1982, ‘Studies on the size, chemical composition and partial sequence of the neuraminidase (NA) from Type A influenza viruses show that the N-terminal region of the NA is not processed and services to anchor the NA in the viral membranes’, Virology, 119: 109-121.

Elleman TC, Azad AA, Ward CW, 1982, ‘Neuraminidase gene from the early Asian strain of human influenza virus, A/R1/5-/57 (H2N2)’, Nucleic Acid Research, 10: 7005-7015.

Ward CW, Elleman TC, Azad AA, 1982, ‘Amino acid sequence of the pronase-released heads of neuraminidase subtypes N2 from the Asian strain A/Tokyo/3/67 of influenza virus’, Biochemical Journal, 27: 91-95.

Colman PM, Gough KH, Lilley GG, Blagrove RJ, Webster RG, Laver WG, 1981, ‘Crystalline monoclonal Fab fragment with specificity towards an influenza virus neuraminidase’, Journal of Molecular Biology, 152: 609-614.