Inhibition of Viral Membrane Fusion by Peptides and Approaches to Peptide Design

Nejat Düzgüneş; Narcis Fernandez-Fuentes; Krystyna Konopka

doi:10.3390/pathogens10121599

Inhibition of Viral Membrane Fusion by Peptides and Approaches to Peptide Design

Pathogens. 2021 Dec 9;10(12):1599. doi: 10.3390/pathogens10121599.

Authors

Nejat Düzgüneş¹, Narcis Fernandez-Fuentes², Krystyna Konopka¹

Affiliations

¹ Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94103, USA.
² Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3EE, UK.

Abstract

Fusion of lipid-enveloped viruses with the cellular plasma membrane or the endosome membrane is mediated by viral envelope proteins that undergo large conformational changes following binding to receptors. The HIV-1 fusion protein gp41 undergoes a transition into a "six-helix bundle" after binding of the surface protein gp120 to the CD4 receptor and a co-receptor. Synthetic peptides that mimic part of this structure interfere with the formation of the helix structure and inhibit membrane fusion. This approach also works with the S spike protein of SARS-CoV-2. Here we review the peptide inhibitors of membrane fusion involved in infection by influenza virus, HIV-1, MERS and SARS coronaviruses, hepatitis viruses, paramyxoviruses, flaviviruses, herpesviruses and filoviruses. We also describe recent computational methods used for the identification of peptide sequences that can interact strongly with protein interfaces, with special emphasis on SARS-CoV-2, using the PePI-Covid19 database.

Keywords: 6-helix bundle; HIV-1; SARS-CoV-2; coiled coil; computation methods; influenza; peptide design; virus entry.

Publication types

Review