Peptide inhibitors of flavivirus entry derived from the E protein stem |
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Authors: | Schmidt Aaron G Yang Priscilla L Harrison Stephen C |
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Affiliation: | Jack and Eileen Connors Structural Biology Laboratory, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., Boston, MA 02115, USA. |
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Abstract: | Peptides derived from the "stem" of dengue virus (DV) type 2 (DV2) envelope (E) protein inhibit DV2 infectivity, targeting a late-stage fusion intermediate. We show here that stem peptides from all DV serotypes cross-inhibit DV1 to DV4 but that corresponding peptides derived from related flaviviruses do not. This failure to inhibit infection is not due to poor interaction with the E protein but rather to loss of association with the virion membrane. Residues 442 to 444 of the stem are determinants of inhibition; increasing hydrophobicity in this region increases inhibitory strength. These results support a two-step model of how stem-derived peptides inhibit viral entry. |
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