Peptide inhibition of human cytomegalovirus infection

Melnik, Lilia I; Garry, Robert F; Morris, Cindy A

Akkarawongsa and coworkers prepared a library of overlapping peptides homologous to the ectodomain of Herpes Simplex Virus Type 1 (HSV-1) gB-1 and screened for the ability of these peptides to block infection [50] . Seven out of 138 15-mer peptides inhibited infection by more than 50% at a concentration of 100 μM. Three peptides (gB131, gB122 and gB94) with 50% effective concentrations below 20 μM were studied further. Peptide gB131 (residues 681 to 695 in HSV-1 gB-1) was identified as a specific entry inhibitor (EC 50 , 12 μM). The gB122 peptide (residues 636 to 650 in gB-1) blocked viral entry (EC 50 ,~18 μM), protected cells from infection (EC 50 ,~72 μM), and inactivated virions in solution (EC 50 ,~138 μM). Of the seven inhibitory peptides identified in the Akkarawongsa et al. study, three of them, corresponding to residues 346 to 360 (gB64), 436 to 450 (gB82), and 636 to 650 (gB122), were in regions of HSV-1 gB-1 with positive WWIHS scores. The success of their study affirms our strategy of targeting the WWIHS score-positive sequences as inhibitors of HCMV. Two overlapping peptides spanning the residues 496 to 510 (gB94) and 501 to 515 (gB95)