Peptide inhibitors of flavivirus entry derived from the E protein stem.
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.
Schmidt
Aaron G
AG
Jack and Eileen Connors Structural Biology Laboratory, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., Boston, MA 02115, USA.
Yang
Priscilla L
PL
Harrison
Stephen C
SC
D000330:Aedes / Q000187:drug effects / Q000821:virology*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003715:Dengue / Q000188:drug therapy* / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D012703:Serotyping; D014759:Viral Envelope Proteins / Q000494:pharmacology*; D014771:Virion / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects*
D010446:Peptide Fragments; D014759:Viral Envelope Proteins