A Peptide Inhibitor Derived from the Conserved Ectodomain Region of DENV Membrane (M) Protein with Activity Against Dengue Virus Infection

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, MLH 40 peptide, for DENV inhibition assays. MLH 40 inhibited all four serotypes of the virus ( DENV 1–4) at half maximal inhibition concentration of 24–31  μ m . MLH 40 at 100  μ m blocked DENV 2 attachment to cells by 80%. The inhibitory activity of MLH 40 against DENV was consistently observed with different cell types, including Vero, A549, and Huh7 cells. Prediction of MLH 40 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, MLH 40 may serve as a lead‐peptide inhibitor for the development of an anti‐ DENV drug.