The Symmetry of Viral Sialic Acid Binding Sites-Implications for Antiviral Strategies.

Rustmeier Rustmeier,Stehle Stehle,Strebl Strebl

doi:10.3390/v11100947

Rustmeier Rustmeier, Stehle Stehle + Show 1 more

Open Access

https://doi.org/10.3390/v11100947

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Journal: Viruses	Publication Date: Oct 14, 2019
Citations: 90	License type: CC BY 4.0

Affiliation: University of Tübingen, Vanderbilt University

Abstract

Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number of diverse viruses. Structural biology research has helped to establish the molecular bases for many virus–sialic acid interactions. Due to the icosahedral 532 point group symmetry that underlies many viral capsids, the receptor binding sites are frequently arranged in a highly symmetric fashion and linked by five-fold, three-fold, or two-fold rotation axes. For the inhibition of viral attachment, one emerging strategy is based on developing multivalent sialic acid-based inhibitors that can simultaneously engage several of these binding sites, thus binding viral capsids with high avidity. In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors.

Highlights

The cell membranes of eukaryotes are decorated with a large number of chemically and structurally diverse carbohydrates
Many members of the polyomavirus family bind sialic acid-based glycans using their VP1 proteins, so the binding sites on individual pentamers are always linked by local five-fold symmetry (Figure 4a, Trichodysplasia spinulosa-associated Polyomavirus (TSPyV))
This review focuses on non-enveloped viruses, it should still be mentioned that some of the concepts described above apply to enveloped viruses, such as coronaviruses, paramyxoviruses, and orthomyxoviruses

Summary

Introduction

The cell membranes of eukaryotes are decorated with a large number of chemically and structurally diverse carbohydrates. Glycans terminating in sialic acid are prominently expressed at the cell surface They are, often accessible and serve as the initial contact points for many viruses in different families [6,7]. Affinity measurements showed an increase in the inhibition potency from a millimolar affinity for the monovalent receptor (pk trisaccharide) to a subnanomolar affinity for the STARFISH compound This concept of targeting multiple, symmetric receptor binding sites by multivalent inhibitors is applicable for many viruses, since viral capsids are often icosahedral and, highly symmetric structures. All protein representations in the figures of this review were generated using PyMOL (Schrödinger Inc.)

Symmetry in Virus Structures and Their Sialic Acid Binding Sites

Monovalency

Polyvalency

Oligovalency

Conclusions