Drug Repositioning for Hand, Foot, and Mouth Disease

Abstract

Hand, foot, and mouth disease (HFMD) is a highly contagious disease in children caused by a group of enteroviruses. HFMD currently presents a major threat to infants and young children because of a lack of antiviral drugs in clinical practice. Drug repositioning is an attractive drug discovery strategy aimed at identifying and developing new drugs for diseases. Notably, repositioning of well-characterized therapeutics, including either approved or investigational drugs, is becoming a potential strategy to identify new treatments for virus infections. Various types of drugs, including antibacterial, cardiovascular, and anticancer agents, have been studied in relation to their therapeutic potential to treat HFMD. In this review, we summarize the major outbreaks of HFMD and the progress in drug repositioning to treat this disease. We also discuss the structural features and mode of action of these repositioned drugs and highlight the opportunities and challenges of drug repositioning for HFMD.

Inhibition of lysosome-tethered Ragulator-Rag-3D complex restricts the replication of Enterovirus 71 and Coxsackie A16

“…HFMD is considered a significant public health threat to infants and young children due to the lack of specific antiviral drugs approved for its treatment ( Lim et al, 2020 ). Although there has been progress toward the development of antiviral drugs against EV71 by targeting viral proteins or host factors ( Lim et al, 2020 ; Yan et al, 2022 ), these are not yet clinically available, and there remains an urgent need to develop effective therapies. We found that ZHSI-1 binds to EV71 3D and reduces the recruitment of 3D to lysosome-tethered Ragulator-Rag.…”

Circular RNA vaccine in disease prevention and treatment

“…Viral infections occur when viruses invade the body and replicate in target cells, leading to an inflammatory host response to viral infection and resulting in target organ tissue damage and dysfunction. 212 The current countermeasures in preventing and treating viral infection, such as SARS-CoV-2 virus, influenza virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), respiratory syncytial virus (RSV), and varicella-zoster virus (VZV), have limited efficacy, despite the existence of antiviral drugs. These are probably attributable to its high infectious capacity and its marked immunogenicity and mutagenic plasticity.…”

Application value of EV/EV71/CA16-SAT detection in children with hand-foot-mouth disease

“…According to data from the Chinese Center for Disease Control and Prevention in June 2018, the number of reported cases of HFMD and the number of deaths in China rank first among C infectious diseases (4). At present, there is no specific drug for HFMD treatment (2). From January 2017 to December 2019, a total of 3492 children with HFMD were diagnosed and treated in our hospital, ranking first among children's infectious diseases in our hospital.…”

“…The common clinical manifestations of HFMD in children are fever with hands and feet, and oral, and buttocks rash, some cases may have no fever, but severe cases may have a series of clinical manifestations such as nervous system involvement, and respiratory and circulatory dysfunction (1). HFMD can be caused by more than 20 kinds of EV, among which coxsackievirus group 16 (CA16) and enterovirus 71 (EV71) are important pathogens of many large-scale outbreaks of HFMD around the world, and EV71 is also the absolutely dominant pathogen causing the death of severe cases of HFMD (2,3). According to data from the Chinese Center for Disease Control and Prevention in June 2018, the number of reported cases of HFMD and the number of deaths in China rank first among C infectious diseases (4).…”