Investigational drugs in early development for treating dengue infection

ABSTRACT

Introduction: Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development.

Areas covered: This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization’s International Clinical Trials Registry Platform web portal using the search term ‘dengue’ on December 31^st, 2015.

Expert opinion: None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict ‘high-risk’ patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

KEYWORDS:

• Dengue virus
• antiviral drugs
• clinical trials
• re-purposing
• antimalarial
• antihelminthic
• corticosteroids
• lovastatin
• balapiravir
• celgosivir

Article highlights

• Dengue is a very significant public health concern of the century.

• It is a mosquito-borne viral disease infecting ~400 million people each year; close to a million of these infections can be potentially fatal.

• Supportive care under trained medical supervision is the only treatment available; a dengue drug is an urgent need.

• Conventional drug discovery efforts have not so far produced any promising leads.

• Old drugs for other indications are being re-purposed for dengue to accelerate dengue drug development.

• Early clinical trials data are not very encouraging; clinical trials have underscored the hurdles in dengue drug development.

• Significant resources and efforts are required before a safe, effective and inexpensive dengue drug becomes available.

This box summarizes key points contained in the article.

Acknowledgment

The authors acknowledge assistance from L Ramakrishnan of BITS Pilani, Hyderabad Campus, for her help with data collection.

Declaration of interest

S Swaminathan is funded by the Department of Biotechnology of the Government of India and the OPERA award from BITS Pilani. Furthermore, H Beesetti is the recipient of the INSPIRE senior research fellowship from the Department of Science & Technology of the Government of India. N Khanna is an employee of the International Centre for Genetic Engineering & Biotechnology, Recombinant Gene Products Group. 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.