The structure of human rhinovirus 16

Area of Science:

• Virology
• Structural Biology
• Drug Discovery

Background:

• Rhinoviruses and polioviruses possess hydrophobic pockets near receptor-binding sites, often containing unknown factors.
• Antiviral compounds can bind to these pockets, displacing factors and inhibiting viral uncoating.
• Human rhinovirus (HRV)14, using ICAM-1, has an empty pocket; antiviral binding deforms it, blocking receptor attachment.

Purpose of the Study:

• To investigate the role of the pocket factor in HRV infectivity.
• To determine the atomic structure of HRV16 and analyze its pocket factor.
• To understand how antiviral compounds interact with HRV pockets and affect receptor binding.

Main Methods:

• X-ray crystallography to determine the atomic resolution structure of HRV16.
• Analysis of electron density within the HRV16 pocket.
• Observation of antiviral compound (WIN 56291) binding to HRV16 and its effect on receptor attachment.

Main Results:

• The structure of HRV16 revealed a pocket containing electron density consistent with a fatty acid (≥8 carbons).
• Unlike HRV14, WIN 56291 binding to HRV16 did not deform the pocket.
• WIN 56291 binding still prevented receptor attachment in HRV16.

Conclusions:

• Receptor binding to HRV16 likely requires a temporarily empty pocket, allowing canyon floor deformation.
• The pocket factor may stabilize the virus during intercellular transit.
• ICAM-1 binding to HRV16 may trap the pocket in an empty state, promoting viral destabilization and uncoating.