Targeting Chikungunya virus by computational approaches: from viral biology to the development of therapeutic strategies

ABSTRACT

Introduction: Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, a reemerging infectious disease. This disease can cause severe manifestations that persist for months or years after acute infection and alas, there are no antiviral drugs or vaccines available. Hence, the development of new therapeutic approaches is necessary.

Areas covered: We review how computational tools have provided insights on CHIKV proteins and examine the advances in the development of potential and novel antiviral drugs. A literature search was performed using PubMed and ScienceDirect databases up to April 2019.

Expert opinion: Computational approaches are valuable for gaining insights into CHIKV proteins and for the design of new anti-CHIKV agents. The collaboration between computational and experimental researchers should be strengthened so that new agents can be developed in a more rational manner. Computer-aided tools could assist in the discovery and development of safer and more efficacious novel antiviral agents from unexplored chemical spaces. Technological advances dictate that this is likely to emerge soon, thus boosting interest and research on CHIKV biology and drug, vaccine and diagnostics development.

KEYWORDS:

• Chikungunya
• bioinformatics
• molecular modeling
• antiviral
• drugs

Article highlights

• Chikungunya fever is caused by the Chikungunya virus (CHIKV) and is a reemerging disease that has spread globally. Despite its impact on the human quality of life, there are no antiviral drugs available to treat this disease.

• Computational techniques have shed light on the structure and function relationship of the many CHIKV proteins that are potential therapeutic targets.

• Computational strategies have guided the discovery and design of several anti-CHIKV compounds targeting several viral proteins. Among these strategies, in silico bioprospecting of natural products and drug repurposing studies have been reported. However, many of these drug candidates need further investigation via in vitro assays.

• The nsP2 protein was the most targeted CHIKV protein by computational strategies and three different binding pockets were explored in drug discovery campaigns. Experimental findings confirmed the existence of allosteric sites within this protein and have paved the way for the design of novel inhibitors.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

The work of the authors was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The work was also supported by Brazilian agencies National Council for Scientific and Technological Development (CNPQ) and Research Support Foundation of the State of Rio de Janeiro (FAPERJ).