Gene

Biology

Viral replication

Pathogen

Virology

Biochemistry

Small interfering RNA

Antiviral drug

Immunology

Polymerase

Internal medicine

Enterovirus 71

Encephalitis

Medicine

Pneumonia

Virus

Enterovirus

Journal of Virology

Human enterovirus (EV) pathogens cause various contagious diseases such as hand, foot, and mouth disease, encephalitis, myocarditis, acute flaccid myelitis, pneumonia, and bronchiolitis, which have become serious health threats. However, except for the EV71 vaccine on the market, there are no effective strategies to prevent and treat other EV pathogen infections. Therefore, broad-spectrum anti-EV drugs are urgently needed. In this study, we demonstrated that FNC, a small nucleoside analog inhibitor that has been demonstrated to be a potent inhibitor of HIV and entered into a clinical phase II trial in China, potently inhibits the viral replication of a multitude of EVs at the nanomolar level. Further investigation revealed that FNC inhibits positive- and negative-strand RNA synthesis of EVs by interacting and interfering with the activity of EV71 viral RNA-dependent RNA polymerase (3D pol ). Our findings demonstrate for the first time that FNC is an effective broad-spectrum inhibitor for human EV pathogens.

The Pyrimidine Analog FNC Potently Inhibits the Replication of Multiple Enteroviruses