title: A peptide inhibitor derived from the conserved ectodomain region of DENV membrane (M) protein with activity against dengue virus infection.
abstract: Dengue virus (DENV) infection is a public health problem worldwide; thus, the development of a vaccine and anti-DENV drugs is urgently needed. It has been observed that low levels of viremia in DENV-infected individuals are associated with mild disease outcomes; therefore, reduction of DENV load should offer therapeutic benefits. Disruption of protein-protein interactions on the surface of DENV by a peptide that mimics part of its structural protein may affect stability of the virion structure and inhibit viral entry into host cells. To test this hypothesis, we generated a novel peptide inhibitor that mimics the conserved ectodomain region of DENV membrane (M) protein, MLH40 peptide, for DENV inhibition assays. MLH40 inhibited all four serotypes of the virus (DENV1-4) at half maximal inhibition concentration of 24-31 μm. MLH40 at 100 μm blocked DENV2 attachment to cells by 80%. The inhibitory activity of MLH40 against DENV was consistently observed with different cell types, including Vero, A549, and Huh7 cells. Prediction of MLH40 binding by a molecular docking program indicated that its N-terminal loop may interact with DENV envelope (E) proteins and alter their dimer conformation. Thus, MLH40 may serve as a lead-peptide inhibitor for the development of an anti-DENV drug.
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.|Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Aussara
authors.initials: A
authors.lastname: Panya
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Nunghathai
authors.initials: N
authors.lastname: Sawasdee
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Mutita
authors.initials: M
authors.lastname: Junking
authors.affiliation: Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Chatchawan
authors.initials: C
authors.lastname: Srisawat
authors.affiliation: Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, 10900, Thailand.
authors.forename: Kiattawee
authors.initials: K
authors.lastname: Choowongkomon
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003715:Dengue / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects; D017434:Protein Structure, Tertiary; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D014759:Viral Envelope Proteins
keywords: Dengue virus; infection; molecular mimicry; peptide inhibitor; public health