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Updated: Jul 9, 2026
Alternative In Vitro Methods for the Determination of Viral Capsid Structural Integrity
Published on: November 16, 2017
Identification of a novel binding inhibitor that blocks the interaction between hSCARB2 and VP1 of enterovirus 71
Qi Tang1,2, Zhichao Xu3, Fan Zhang2
1Department of Microbiology, The Key Laboratory of Microbiology and Parasitology of Anhui Province, The Key Laboratory of Zoonoses of High Institutions in Anhui, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Insights
A novel antiviral drug, PTC-209HBr, effectively inhibits Enterovirus 71 (EV-A71) by blocking viral entry. This discovery offers a promising new treatment for severe EV-A71 infections, addressing a critical unmet medical need.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Enterovirus 71 (EV-A71) causes severe hand-foot-and-mouth disease in young children, with limited treatment options for severe cases.
- Existing vaccines target specific EV-A71 strains, but effective direct-acting antiviral agents (DAAs) for severe infections are lacking.
Purpose of the Study:
- To identify and characterize novel direct-acting antiviral agents (DAAs) for Enterovirus 71 (EV-A71) infection.
- To investigate the mechanism of action of potential EV-A71 inhibitors.
Main Methods:
- Screening of small molecules, including the Bmi-1 inhibitor PTC-209HBr and its derivatives, for antiviral activity against EV-A71.
- Utilizing time-of-addition, resistance selection, reverse genetics, microscale thermophoresis (MST), viral binding and entry assays, coimmunoprecipitation (Co-IP), and immunofluorescence (IF) to elucidate the mechanism of action.
Main Results:
- PTC-209HBr and its derivatives demonstrated submicromolar efficacy in inhibiting multiple enteroviruses, including EV-A71.
- PTC-209HBr was confirmed to inhibit EV-A71 infection by preventing the interaction between viral protein VP1 and the host cell receptor hSCARB2, thus hindering viral entry.
Conclusions:
- PTC-209HBr is a potent inhibitor of EV-A71, acting as a novel capsid inhibitor.
- The identified mechanism of action, targeting early viral entry, positions PTC-209HBr as a promising candidate for further development into effective DAAs against EV-A71.
Abstract:
Enterovirus 71 (EV-A71) infection causes severe hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children under 5 years of age. Although there are available vaccines for EV-A71 C4, however, there are no efficient drugs for severe cases. Thus, there is an urgent need to find new direct-antiviral agents (DAAs) to control EV-A71 infection. In this study, we report our discovery of the EV-A71 capsid inhibitor PTC-209HBr, a small-molecule Bmi-1 inhibitor and an anticancer agent, and its derivatives that inhibit multiple enteroviruses with an EC50 at a submicromolar efficacy. The mechanism of action of PTC-209HBr was confirmed by time-of-addition, resistance selection and reverse genetics experiments, microscale thermophoresis (MST), viral binding and entry assays, coimmunoprecipitation (Co-IP) and immunofluorescence experiments (IF). Mechanistic studies indicated that PTC-209HBr inhibited EV-A71 infection by impeding the binding between VP1 and the receptor hSCARB2 during the early stage of EV-A71 infection through hindering viral entry into host cells. Collectively, these findings indicated that PCT-209HBr is a novel inhibitor of enteroviruses with a confirmed mechanism of action that can be further developed into EV-A71 DAAs.
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