title: Aptamer that binds to the gD protein of herpes simplex virus 1 and efficiently inhibits viral entry.
abstract: The ectodomain of the gD protein of herpes simplex viruses (HSVs) plays an important role in viral entry by binding to specific cellular coreceptors and mediating viral entry to the host cells. In the present study, we isolated RNA aptamers (aptamer-1 and aptamer-5) that specifically bind to the gD protein of HSV-1 with high affinity and are able to discriminate the gD protein of a different virus, HSV-2. Aptamer-1 efficiently interfered with the interaction between the gD protein and the HSV-1 target cell receptor (HVEM) in a dose-dependent manner. The 50% effective concentration (EC(50)) of aptamer-1 was estimated to be in the nanomolar range (60 nM). Furthermore, aptamer-1 was analyzed for anti-HSV-1 activity by using plaque assays, and it efficiently inhibited viral entry with an estimated K(i) of 0.8 μM. To expand the future applications of aptamer-1, a shorter variant was designed by using both mapping and boundary analyses, resulting in the mini-1 aptamer (44-mer). Compared to the full-length aptamer, mini-1 had at least as high an affinity, specificity, and ability to interfere with gD-HVEM interactions. These studies suggest that the mini-1 aptamer could be explored further as an anti-HSV-1 topical therapy designed to prevent the risk of acquiring HSV-1 infection through physical contact.
authors.affiliation: Biomedical Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong, Chinaa.
authors.forename: Subash C B
authors.initials: SC
authors.lastname: Gopinath
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Penmetcha K R
authors.initials: PK
authors.lastname: Kumar
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D015536:Down-Regulation; D006561:Herpes Simplex / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D052157:Aptamers, Nucleotide; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1