Chikungunya virus drug discovery: still a long way to go?

Introduction: Chikungunya virus (CHIKV) is the etiological agent of a (re)emerging arbovirus infection, chikungunya fever (CHIKF), that represents a serious health problem worldwide for which no antivirals are available. Areas covered: This review covers the efforts performed so far to identify and optimize small molecules that could be useful as antivirals for CHIKV infection, including drug repositioning, phenotypic screening, target-based screening, and structure-based design. This is accompanied by a brief presentation of the replicative cycle of the virus and the role of the viral proteins in CHIKV replication. Expert opinion: In the last decade, and particularly since CHIKV reached the Americas, significant efforts have been made to identify compounds that effectively inhibit CHIKV replication. Unfortunately, these efforts have not led to a clinical candidate. For the years to come, more basic research is required to allow a better understanding of the interplay of the viral proteins among them and with cellular components. Structural information is missing for most of the targets so that structure-based drug design, a strategy that has provided good results in other antiviral fields, has been scarcely applied to this alphavirus.