Systematic screening of viral entry inhibitors using surface plasmon resonance.

Abstract

Viral binding and entry into host cells for various viruses have been studied extensively, yielding a detailed understanding of the overall viral entry process. As cell entry is an essential and requisite process by which a virus initiates infection, it is an attractive target for therapeutic intervention. The advantages of targeting viral entry are an extracellular target site, relatively easy access for biological interventions, and lower toxicity. Several cell-based strategies and biophysical techniques have been used to screen compounds that block viral entry. These studies led to the discovery of inhibitors against HIV, HCV, influenza, Ebola, and RSV. In recent years, several compounds screened by fragment-based drug discovery have been approved as drugs or are in the final stages of clinical trials. Among fragment screening technologies, surface plasmon resonance has been widely used because it provides accurate information on binding kinetics, allows real-time monitoring of ligand-drug interactions, requires very small sample amounts to perform analyses, and requires no modifications to or labeling of ligands. This review focuses on surface plasmon resonance-based schemes for screening viral entry inhibitors.