The Chinese University of Hong Kong China.
Title: Inhibition of enterovirus 71 entry by peptides targeting I β-sheet of VP1 protein
Dr He received his Bachelor of Science degree from Sichuan University (Biochemistry). After graduation in 1998, he worked as an engineer in a pharmaceutical factory in Chongqin. He obtained his PhD degree from Shanghai Institute of Biochemistry (and Cell Biology) in 1995. He obtained his postdoctoral training in Roswell Park Cancer Institute at Buffalo (1995–1997) and Washington University School of Medicine at St. Louis in USA (1997–2000). He joined The University of Hong Kong (Institute of Molecular Biology) as Research Assistant Professor in 2000. After SARS outbreak in Hong Kong in 2003, He was appointed as Associate Professor (2005–2011) and Research Associate Professor (2011–2015, Policy Change) at Stanley Ho Center for Emerging Infectious Disease, Faculty of Medicine, The Chinese University of Hong Kong. He joined Department of Biomedical Sciences at City University of Hong Kong in February 2015
The binding of enterovirus capsid protein VP1 on the host receptors is the first step for virus entry during the infection. Peptides blocking the binding of VP1 and its receptors can be used not only for antiviral treatment but also for probing functional important motifs or residues involved in this biological process. Based on the crystal structure of VP1-VP4 complex of enterovirus 71 (EV71), we applied molecular modeling approaches to revisit the potential antiviral peptides in an anti-enterovirus 71 screening study. We showed that a β-sheet structure (I β) is unique and locates at a very favorable position for drug target. More importantly, the sequence of I β-sheet is highly conserved among subtypes of EV71, suggesting an idea target sites for antiviral drug design. Peptides targeting I β-sheet potently inhibited EV71 infections. Further attachment and single-round pseudovirus infection assays revealed that the attachment of virions on host cells was effectively blocked by peptides. Alanine scan analysis demonstrated that residues Arg250, Arg254, Met255 and Lys256 are critical for virion binding on host cells. This study demonstrated the importance of I β-sheet structure for EV71 entry and an effective peptide for block virion-host cell interactions.
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