Enterovirus A71 antivirals: Past, present, and future

Enterovirus A71 (EV-A71) is a significant human pathogen, especially in children. EV-A71 infection is one of the leading causes of hand, foot, and mouth diseases (HFMD), and can lead to neuro-logical complications such as acute flaccid myelitis (AFM) in severe cases. Although three EV-A71 vac-cines are available in China, they are not broadly protective and have reduced efficacy against emerging strains. There is currently no approved antiviral for EV-A71. Significant progress has been made in devel-oping antivirals against EV-A71 by targeting both viral proteins and host factors. However, viral capsid inhibitors and protease inhibitors failed in clinical trials of human rhinovirus infection due to limited ef-ficacy or side effects. This review discusses major discoveries in EV-A71 antiviral development, analyzes the advantages and limitations of each drug target, and highlights the knowledge gaps that need to be addressed to advance the field forward. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.