Antivirals targeting paramyxovirus membrane fusion

Abstract

The Paramyxoviridae family includes enveloped single-stranded negative-sense RNA viruses such as measles, mumps, human parainfluenza, canine distemper, Hendra, and Nipah viruses, which cause a tremendous global health burden. The ability of paramyxoviral glycoproteins to merge viral and host membranes allows entry of the viral genome into host cells, as well as cell-cell fusion, an important contributor to disease progression. Recent molecular and structural advances in our understanding of the paramyxovirus membrane fusion machinery gave rise to various therapeutic approaches aiming at inhibiting viral infection, spread, and cytopathic effects. These therapeutic approaches include peptide mimics, antibodies, and small molecule inhibitors with various levels of success at inhibiting viral entry, increasing the potential of effective antiviral therapeutic development.

Figure 1

Summary of Paramyxovirus antiviral target locations within the membrane fusion cascade model. Green bars indicate anti-paramyxovirus antibody epitopes, Red bars show peptide targets, and blue bars point to small-molecule antiviral interaction sites. PHI = Pre-hairpin Intermediate, 6HB = 6 Helix Bundle.