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Downard Laboratory WWW site

 

The following publications from this laboratory describe novel, new molecular-based, mass spectrometry approaches to survey the influenza virus, chart its evolutionary history, characterise viral antigenicity and identify new therapeutics. They offer new advantages over conventional molecular and non-molecular approaches currently employed in surveillance and responses to the virus. The approaches are applicable to the study of other biopathogens, the results of which are also reported below.

 

Surveillance (with proteotyping)

 

Uddin R, Downard KM (2017) Subtyping of Hepatitis C Virus with High Resolution Mass Spectrometry, Clin. Mass Spectrom. 4-5: 19-24.

 

Fernandes ND, Downard KM (2014) Incorporation of a Proteotyping Approach using Mass Spectrometry for the Surveillance of the Influenza Virus in Cell Culture, J. Clin. Microbio. 52: 725-735.

Fernandes ND, Downard KM (2014) Origins of the Reassortant H1N1 2009 Pandemic Influenza Virus by Proteotyping with Mass Spectrometry, J. Mass Spectrom. 49: 93-102.

Downard KM (2013) Proteotyping for the Rapid Identification of Pandemic Influenza Virus and other Biopathogens, Chem. Soc. Rev. 42: 8584-8595.

Nguyen AP, Downard KM (2013) Subtyping of Influenza Neuraminidase using Mass Spectrometry, Analyst 138: 1787- 1793.

Nguyen AP, Downard KM (2013) Proteotyping of the Parainfluenza Virus with High Resolution Mass Spectrometry, Anal. Chem.  85: 1097-1105.

Lun ATL, Wong JWH, Downard KM (2012) FluShuffle and FluResort - New Algorithms to Identify Reassorted Strains of the Influenza Virus by Mass Spectrometry, BMC Bioinformatics 13: 208.

Schwahn AB, Wong JWH, Downard KM (2010) Rapid Differentiation of Seasonal and Pandemic H1N1 Influenza through Proteotyping of Viral Neuraminidase with Mass Spectrometry, Anal. Chem. 82: 4584-4590.

Schwahn AB, Wong JWH, Downard KM (2010) Typing of Human and Animal Strains of Influenza Virus with Conserved Signature Peptides of Matrix M1 Protein by High Resolution Mass Spectrometry, J. Virol. Methods 165: 178-185.

Schwahn AB, Wong JWH, Downard KM (2009) Signature peptides of influenza nucleoprotein for the typing and subtyping of the virus by high resolution mass spectrometry, Analyst 134: 2253-2261.

Downard KM, Morrissey B (2007) Fingerprinting a Killer - Surveillance of the Influenza Virus by Mass Spectrometry, Analyst 132: 611-614.

Evolution
 

Akand EH, Downard KM (2019) Mechanisms of Antiviral Resistance in Influenza Neuraminidase Revealed by a Mass Spectrometry Based Phylonumerics Approach, Mol. Phylogen. Evol., 135: 286-296.

 

Akand EH, Downard KM (2018) Ancestral and Compensatory Mutations that Promote Antiviral Resistance in Infulenza N1 Neuraminidase Revealed by a Phylonumerics Approach, J. Mol. Evol. 86: 546-553.

 

Akand EH, Downard KM (2018) Identification of Epistatic Mutations and Insights into the Evolution of the Influenza Virus Using a Mass-Based Protein Phylogenetic Approach, Mol. Phylogen. Evol., 121: 132-138.

 

Akand EH, Downard KM (2017) Mutational Analysis Employing a Phylogenetic Mass Tree Approach in a Study of the Evolution of the Influenza Virus, Mol. Phylogen. Evol. 112: 209-217.

 

Ma S, Wong JWH, Downard KM (2015) A Novel Algorithm and Approach to Score and Visualize the Phylogeny of the Influenza Virus using Mass Spectrometry, Anal. Chim. Acta 895: 54-61.

Swaminathan K, Downard KM (2014) Evolution of Influenza Neuraminidase and the Detection of Antiviral Resistant Strains Using Mass Trees, Anal. Chem. 86: 629-637.

Lun ATL, Swaminathan K, Wong JWH, Downard KM (2013) Mass Trees – A New Phylogenetic Approach and Algorithm to Chart Evolutionary History with Mass Spectrometry, Anal. Chem. 85: 5475-5482.

Ha J-W, Downard KM (2011) Evolution of H5N1 Influenza Virus through Proteotyping of Hemagglutinin with High Resolution Mass Spectrometry, Analyst 136, 3259-3267.

Vaccines

Schwahn AB, Wong JWH, Downard KM (2010) Rapid typing and subtyping of vaccine strains of the influenza virus with high resolution mass spectrometry, Eur. J. Mass Spectrom. 16: 321-329.

Therapeutics
 

Uddin R, Downard KM (2018) Molecular Basis of Benzimidazole Inhibitors to Hepatitis C Virus Envelope Glycoprotein, Chem. Biol. Drug Design 92: 1638-1646.


Maleknia SD, Downard KM (2016) New Anthocyanins from Black Elderberry of Inhibitory Potential Revealed by Mass Spectrometry, Nat. Prod. J. 6: 94-102.

 

Lu R, Muller P, Downard KM (2015) Molecular Basis of Influenza Hemaglutinin Inhibition with an Entry-Blocker Peptide by Computational Docking and Mass Spectrometry, Antiviral Chem. Chemother. 24: 109-117.

Muller P, Downard KM (2015) Catechins Inhibit Influenza Neuraminidase and its Molecular Basis with Mass Spectrometry, J. Pharmaceut. Biomed. Anal. 111: 222-230.

Swaminathan K, Muller P, Downard KM (2014) Substituent Effects on the Binding of Natural Product Anthocyanidin Inhibitors to Influenza Neuraminidase with Mass Spectrometry, Anal. Chim. Acta 828: 61-69.

Nasser Z, Swaminathan K, Muller P, Downard KM (2013) in-vitro Inhibition of the Influenza virus with the Anti-Viral Inhibitor Arbidol by a Proteomics based Approach with Mass Spectrometry, Antiviral Res. 100: 399-406.

Swaminathan K, Dyason JC, Maggioni A, von Itzstein M, Downard KM (2013) Binding of a Natural Anthocyanin Inhibitor to Influenza Neuraminidase by Mass Spectrometry, Anal. Bio. Chem. 405: 6563-6572.

Swaminathan K, Downard KM (2012) Anti-Viral Inhibitor Binding to Influenza Neuraminidase by MALDI Mass Spectrometry, Anal. Chem. 84: 3725-3730.

Viral Antigenicity

Downard KM (2019) A Molecular Immunoproteomics Approach to Assess the Viral Antigenicity of Influenza, in Methods in Molecular Biology: Immunoproteomics: Methods and Protocols, Second Edition (Ed. S. Twine & K. Fulton), in press.

 

Downard KM (2013) An Immunoproteomics Approach to Screen the Antigenicity of the Influenza Virus, in Methods in Molecular Biology: Immunoproteomics (Ed. S. Twine & K. Fulton), Vol. 1061, Ch. 8, pg 141-153.

Schwahn AB, Downard KM (2009) Antigenicity of a type A influenza virus through a comparison of hemagglutination inhibition and mass spectrometry immunoassays, J. Immunoassay Immunochem. 30: 245-261.

Morrissey B, Downard KM (2008) Kinetics of Antigen-Antibody Interactions Employing a MALDI Mass Spectrometry Immunoassay, Anal. Chem. 80: 7720-7726.

Morrissey B, Streamer M, Downard KM (2007) Antigenic Characterisation of H3N2 subtypes of the Influenza Virus by Mass Spectrometry, J. Virol. Methods 145: 106-114.

Morrissey B, Downard KM (2006) A Proteomics Approach to Survey the Antigenicity of the Influenza Virus by Mass Spectrometry, Proteomics 6: 2034-2041.

Kiselar JG, Downard KM (1999) Antigenic Surveillance of the Influenza Virus by Mass Spectrometry, Biochemistry 43: 14185-14191.

 

Software (for Viral Antigenicity and Inhibitor Binding Studies)

Ho JWK, Morrissey B, Downard KM (2007) A Computer Algorithm for the Identification of Protein Interactions from the Spectra of Masses (PRISM), J. Am. Soc. Mass Spectrom., 18, 563– 566. 

 

Mimetics

Downard KM (1997) Characterization of the Conformations of Antigenic Peptides of Protein Lactate Dehydrogenase (LDH-C4) by Electrospray Ionization Mass Spectrometry, Rapid Commun. Mass Spectrom. 11: 1853-1858.

Additional Reviews

Downard KM, Morrissey B, Schwahn AB (2009) Mass Spectrometry Analysis of the Influenza Virus, Mass Spectrom. Rev. 28: 35-49.

 

Downard K.M. (2000) Contributions of Mass Spectrometry to Structural Immunology, J. Mass Spectrom. 35: 493-503.

Related Methodology Development (and Reviews thereof)

Downard KM (2016) Indirect Study of Non-Covalent Protein Complexes by MALDI Mass Spectrometry. Origins, Advantages and Applications of the "Intensity-Fading" Approach, Mass Spectrom. Rev. 35: 559-573.

 

Downard KM (2007) Softly. Softly. Detection of Protein Complexes by Matrix-assisted Laser Desorption Ionization Mass Spectrometry, in Mass Spectrometry of Protein Interactions, Downard KM (ed.), John Wiley & Sons, New Jersey U.S.A., pp. 25-43.

Mackun K., Downard KM (2003) Strategy for the Study of Protein-Protein Interactions of Gel- Separated Proteins by Mass Spectrometry, Anal. Biochem. 318: 60-70.

 

Kiselar JG, Downard KM (2001) Preservation of Specific Immune Complexes by Matrix-assisted Laser Desorption Ionization Mass Spectrometry, in Advances in Mass Spectrometry, Volume 15, E. Gelphi (ed.) John Wiley & Sons, Chichester, UK.

 

Kiselar JG, Downard KM (1999) Direct Identification of Protein Epitopes by Mass Spectrometry without Immobilization of Antibody and Isolation of Antibody-Peptide Complexes, Anal. Chem. 17: 1792-1801.

 

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 INFLUENZA RESEARCH