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Literature DB >> 28217261

Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited.

Antonios Drakopoulos¹, Christina Tzitzoglaki¹, Chulong Ma², Kathrin Freudenberger³, Anja Hoffmann⁴, Yanmei Hu², Günter Gauglitz³, Michaela Schmidtke⁴, Jun Wang², Antonios Kolocouris¹.

Abstract

Recent findings from solid state NMR (ssNMR) studies suggested that the (R)-enantiomer of rimantadine binds to the full M2 protein with higher affinity than the (S)-enantiomer. Intrigued by these findings, we applied functional assays, such as antiviral assay and electrophysiology (EP), to evaluate the binding affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly, no significant difference was found between the two enantiomers. Our experimental data based on the full M2 protein function were further supported by alchemical free energy calculations and isothermal titration calorimetry (ITC) allowing an evaluation of the binding affinity of rimantadine enantiomers to the M2TM pore. Both enantiomers have similar channel blockage, affinity, and antiviral potency.

Entities: Chemical

Keywords: Bennett’s acceptance ratio; Rimantadine enantiomers; antiviral assay; electrophysiology; free energy perturbation; influenza M2 pore; isothermal titration calorimetry; membrane protein; synthesis

Year: 2017 PMID： 28217261 PMCID： PMC5312807 DOI： 10.1021/acsmedchemlett.6b00311

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

36 in total

1. Membrane-dependent effects of a cytoplasmic helix on the structure and drug binding of the influenza virus M2 protein.

Authors: Sarah Cady; Tuo Wang; Mei Hong
Journal: J Am Chem Soc Date: 2011-07-07 Impact factor: 15.419

2. Hydrogen-bonded water molecules in the M2 channel of the influenza A virus guide the binding preferences of ammonium-based inhibitors.

Authors: Eleonora Gianti; Vincenzo Carnevale; William F DeGrado; Michael L Klein; Giacomo Fiorin
Journal: J Phys Chem B Date: 2014-11-11 Impact factor: 2.991

3. Specific binding of adamantane drugs and direction of their polar amines in the pore of the influenza M2 transmembrane domain in lipid bilayers and dodecylphosphocholine micelles determined by NMR spectroscopy.

Authors: Sarah D Cady; Jun Wang; Yibing Wu; William F DeGrado; Mei Hong
Journal: J Am Chem Soc Date: 2011-03-07 Impact factor: 15.419

4. Design and pharmacological characterization of inhibitors of amantadine-resistant mutants of the M2 ion channel of influenza A virus.

Authors: Victoria Balannik; Jun Wang; Yuki Ohigashi; Xianghong Jing; Emma Magavern; Robert A Lamb; William F Degrado; Lawrence H Pinto
Journal: Biochemistry Date: 2009-12-22 Impact factor: 3.162

5. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells.

Authors: I V Chizhmakov; F M Geraghty; D C Ogden; A Hayhurst; M Antoniou; A J Hay
Journal: J Physiol Date: 1996-07-15 Impact factor: 5.182

Review 6. Clinical applications of antiviral agents for chemophrophylaxis and therapy of respiratory viral infections.

Authors: F G Hayden
Journal: Antiviral Res Date: 1985 Impact factor: 5.970

7. Synthesis and antiviral activity of metabolites of rimantadine.

Authors: P S Manchand; R L Cerruti; J A Martin; C H Hill; J H Merrett; E Keech; R B Belshe; E V Connell; I S Sim
Journal: J Med Chem Date: 1990-07 Impact factor: 7.446

8. Synthesis and antiviral activity evaluation of some aminoadamantane derivatives.

Authors: N Kolocouris; G B Foscolos; A Kolocouris; P Marakos; N Pouli; G Fytas; S Ikeda; E De Clercq
Journal: J Med Chem Date: 1994-09-02 Impact factor: 7.446

9. Free Energy Calculations Reveal the Origin of Binding Preference for Aminoadamantane Blockers of Influenza A/M2TM Pore.

Authors: Paraskevi Gkeka; Stelios Eleftheratos; Antonios Kolocouris; Zoe Cournia
Journal: J Chem Theory Comput Date: 2013-01-03 Impact factor: 6.006

10. Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds.

Authors: Eva Torres; María D Duque; Evelien Vanderlinden; Chunlong Ma; Lawrence H Pinto; Pelayo Camps; Mathy Froeyen; Santiago Vázquez; Lieve Naesens
Journal: Antiviral Res Date: 2013-06-22 Impact factor: 5.970

7 in total

1. Unraveling the Binding, Proton Blockage, and Inhibition of Influenza M2 WT and S31N by Rimantadine Variants.

Authors: Antonios Drakopoulos; Christina Tzitzoglaki; Kelly McGuire; Anja Hoffmann; Athina Konstantinidi; Dimitrios Kolokouris; Chunlong Ma; Kathrin Freudenberger; Johanna Hutterer; Günter Gauglitz; Jun Wang; Michaela Schmidtke; David D Busath; Antonios Kolocouris
Journal: ACS Med Chem Lett Date: 2018-01-29 Impact factor: 4.345

Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited.

1. Membrane-dependent effects of a cytoplasmic helix on the structure and drug binding of the influenza virus M2 protein.

2. Hydrogen-bonded water molecules in the M2 channel of the influenza A virus guide the binding preferences of ammonium-based inhibitors.

3. Specific binding of adamantane drugs and direction of their polar amines in the pore of the influenza M2 transmembrane domain in lipid bilayers and dodecylphosphocholine micelles determined by NMR spectroscopy.

4. Design and pharmacological characterization of inhibitors of amantadine-resistant mutants of the M2 ion channel of influenza A virus.

5. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells.

Review 6. Clinical applications of antiviral agents for chemophrophylaxis and therapy of respiratory viral infections.

7. Synthesis and antiviral activity of metabolites of rimantadine.

8. Synthesis and antiviral activity evaluation of some aminoadamantane derivatives.

9. Free Energy Calculations Reveal the Origin of Binding Preference for Aminoadamantane Blockers of Influenza A/M2TM Pore.

10. Role of the viral hemagglutinin in the anti-influenza virus activity of newly synthesized polycyclic amine compounds.

1. Unraveling the Binding, Proton Blockage, and Inhibition of Influenza M2 WT and S31N by Rimantadine Variants.

2. Increased Dissociation of Adamantanamines in Influenza A M2 S31N with Partial Block by Rimantadine.

3. Inhibitors of the M2 Proton Channel Engage and Disrupt Transmembrane Networks of Hydrogen-Bonded Waters.

Review 4. Metabolic host response and therapeutic approaches to influenza infection.

5. Bayesian regression and model selection for isothermal titration calorimetry with enantiomeric mixtures.

6. Rimantadine Binds to and Inhibits the Influenza A M2 Proton Channel without Enantiomeric Specificity.

Review 7. Put a cork in it: Plugging the M2 viral ion channel to sink influenza.