Virus−Ligand Interactions:  Identification and Characterization of Ligand Binding by NMR Spectroscopy

• Published in: Journal of the American Chemical Society Vol. 125; no. 1; pp. 14 - 15
• Main Authors: Benie, Andrew J, Moser, Rosita, Bäuml, Englbert, Blaas, Dieter, Peters, Thomas
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08-01-2003
• Subjects: Analytical chemistry; Antiviral Agents - chemistry; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Binding Sites; Chemistry; Exact sciences and technology; Human rhinovirus 2; Humans; Isoxazoles - chemistry; Isoxazoles - metabolism; Isoxazoles - pharmacology; Kinetics; Ligands; Nuclear Magnetic Resonance, Biomolecular - methods; Rhinovirus - chemistry; Rhinovirus - drug effects; Rhinovirus - metabolism; Spectrometric and optical methods; Substrate Specificity; Virus; Characterization; Analytical chemistry; Binding; Picornaviridae; Antiviral; Saturation transfer; Identification; NMR spectrometry; Human rhinovirus; Rhinovirus
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja027691e

We demonstrate the detection and characterization of ligand binding to viruses via NMR. To illustrate the methodology, the interaction of an antiviral compound with human rhinovirus serotype 2 (HRV2) was investigated. Specific interaction of a capsid-binding inhibitor and native HRV2 was monitored utilizing saturation transfer difference (STD) NMR. STD NMR experiments at atomic resolution allowed those regions of the ligand that are involved in the interaction with the virus to be determined. The approach allows for (i) the fast and robust assessment of binding, (ii) the determination of the ligand binding epitope at atomic resolution without the necessity to crystallize virus−ligand complexes, and (iii) the reuse of the virus in subsequent assays. This methodology enables one to easily identify binding of drugs, peptides, and receptor or antibody fragments to the viral capsid.