International Society for Antiviral Research

Antiviral drug discovery: a multifactorial and challenging endeavour

María Jesús Pérez Pérez, PhD

Instituto de Química Médica (IQM, CSIC), Madrid, Spain

Despite the success in developing effective antivirals for some viral infections (i.e. HIV or HCV), there is still an urgent unmet need for novel compounds to fight viral diseases. Drug discovery has become a multifactorial endeavour where different disciplines including medicinal chemistry, molecular biology, computational chemistry or toxicology, need to be integrated with the final aim to identify the best compound(s) to be progressed towards development. In addition, the input of new disciplines such as artificial intelligence, “omics” sciences or delivery systems is expected to significantly contribute to this aim. Still the exponential growth of chemical and biological data can lead to a wealth of information that can slow down the research process if not correctly managed for improving decision-making. In this multifactorial scenario, antiviral drug discovery includes an additional particularity compared to other therapeutic fields: the interplay of the virus and the host. While most of the antivirals developed so far have been directed towards viral targets, host factors are increasingly being addressed in this field. Additionally, phenotypic screening is still the main source for small molecules clinical candidates for viral infections, while for other therapeutic areas target- or fragment-based screening are gaining importance. In this complex scenario, the quality of the chemical compounds is crucial for increasing the likelihood of drug approval. Thus, medicinal chemistry plays a key role in the identification of the right hit compounds and their progression towards a good lead for preclinical studies, as will be illustrated with recent examples in antiviral drug discovery.