A Novel Peptide from VP1 of EV-D68 Exhibits Broad-Spectrum Antiviral Activity Against Human Enteroviruses
Xiaojing Lin,
Qiang Sun,
Yang Cao,
Zi Li,
Cuiling Xu,
Jun Liu,
Jingdong Song,
Kun Qin,
Yong Zhang,
Jianfang Zhou
Affiliations
Xiaojing Lin
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Qiang Sun
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Yang Cao
Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China
Zi Li
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Cuiling Xu
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Jun Liu
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Jingdong Song
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Kun Qin
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Yong Zhang
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Jianfang Zhou
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Enteroviruses have been a historical concern since the identification of polioviruses in humans. Wild polioviruses have almost been eliminated, while multiple species of non-polio enteroviruses and their variants co-circulate annually. To date, at least 116 types have been found in humans and are grouped into the species Enterovirus A–D and Rhinovirus A–C. However, there are few available antiviral drugs, especially with a universal pharmaceutical effect. Here, we demonstrate that peptide P25 from EV-D68 has broad antiviral activity against EV A–D enteroviruses in vitro. P25, derived from the HI loop and β-I sheet of VP1, operates through a conserved hydrophilic motif -R---K-K--K- and the hydrophobic F near the N-terminus. It could prevent viral infection of EV-A71 by competing for the heparan sulfate (HS) receptor, binding and stabilizing virions by suppressing the release of the viral genome. P25 also inhibited the generation of infectious viral particles by reducing viral protein synthesis. The molecular docking revealed that P25 might bind to the pocket opening area, a potential target for broad-spectrum antivirals. Our findings implicate the multiple antiviral effects of peptide P25, including blocking viral binding to the HS receptor, impeding viral genome release, and reducing progeny particles, which could be a novel universal anti-enterovirus drug candidate.