Recent progress and challenges in drug development to fight hand, foot and mouth disease

ABSTRACT

Introduction: Hand, foot and mouth disease (HFMD) is a serious public health concern in the Asia-Pacific region with recurrent cyclical outbreaks. Enterovirus 71 (EV-A71) and coxsackievirus type A are the main causative agents of HFMD. While majority of HFMD cases are mild and self-limiting, neurological complications have been reported for EV-A71 associated HFMD. There is currently no effective treatment against HFMD and monovalent vaccines against EV-A71 are currently limited to the Chinese market.

Areas covered: As of today, HFMD antiviral development has focused on EV-A71 and involves conventional screening of drug libraries. In recent years, attention has shifted toward identifying druggable host factors to avoid drug resistance and identify drug candidates with broader antiviral activity across EV-A71 genogroups and other HFMD causative agents.

Expert opinion: The effective development of HFMD interventions requires us to address the gaps in our understanding of its pathogenesis at the molecular level. The limited resources devoted to the development of HFMD treatment strategies worldwide also contribute to the slow progress of promising drug and vaccine candidates along the clinical pipeline.

KEYWORDS:

• Drug library screen
• enterovirus 71 (ev-a71)
• hand
• foot and mouth disease (hfmd)
• host targeting antivirals (HTAs)

Article Highlights

• HFMD is of major concern in the Asia-Pacific region with sporadic outbreaks throughout the year.

• HFMD caused by EV-A71 strains can lead to life-threatening neurological complications.

• The lack of treatment options against EV-A71 makes drug development a priority.

• Screening of various drug libraries has led to the identification of a number of promising drug candidates, but their full pre-clinical validation has yet to be reported.

• Identification of druggable host factors exploited by EV-A71 during its infection cycle represents a promising approach in the development of broad-spectrum anti-EV-A71 antivirals with lower chance of drug resistance.

• Greater awareness and support from various stakeholders are needed to tackle HFMD effectively.

This box summarizes the key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors are supported by Singapore’s Ministry of Health via the National Medical Research Council (Grant No. NMRC/CBRG/0098/2015).