LAUSR

ABSTRACT Dengue virus (DENV) infection has become a severe public health problem worldwide. However, there is no specific antiviral drug available yet. In this study, we found that DENV serotype 2 (DENV2) infection enhanced the expression of &bgr;3 integrin on human umbilical vein endothelial cells (HUVECs) and that DENV2 antigens co‐localized with &bgr;3 integrin. DENV2 envelope protein (E) directly interacted with &bgr;3 integrin, and their interacting sites were located at domain III of E protein (EDIII). Several synthetic peptides were designed based on the amino acid sequence of EDIII, and peptides P4 and P7 could inhibit DENV2 entry into HUVECs in a dose‐dependent manner. The inhibitory concentration (IC50) of the two peptides was 19.08 ± 2.52 &mgr;M for P4 and 12.86 ± 5.96 &mgr;M for P7. Moreover, P7 containing an FG‐loop, but not P4, could also inhibit DENV1 entry into HUVECs. Our results suggest a novel mechanism in which interaction between &bgr;3 integrin and EDIII is involved in DENV entry. The findings on the inhibitory effect of the peptides on viral entry have significance for anti‐DENV drug design. HighlightsDENV2 E directly interacted with &bgr;3 integrin.The binding sites located at regions of C333‐V347 and G381‐K394 of EDIII.P4 and P7 could block DENV2 entry via interacting with &bgr;3 integrin.