Key result
Multi-target directed ligand strategies highlight novel antiviral candidates for non-polio enterovirus infections.
Why the study?
No approved treatments exist for non-polio enteroviruses and single-molecule clinical trials have failed, prompting evaluation of the multi-target directed ligand strategy.
Systematic Review
The multi-target directed ligand strategy may provide a novel pathway to develop effective treatments for non-polio enterovirus infections, which have historically failed in clinical trials using single-target approaches.
May guide future antiviral design for non-polio enteroviruses; extends single-target trial data by advocating multi-target ligands to reduce resistance.
Non-polio enteroviruses (NPEVs), namely coxsackieviruses (CV), echoviruses (E), enteroviruses (EV), and rhinoviruses (RV), are responsible for a wide variety of illnesses. Some infections can progress to life-threatening conditions in children or immunocompromised patients. To date, no treatments have been approved. Several molecules have been evaluated through clinical trials without success. To overcome these failures, the multi-target directed ligand (MTDL) strategy could be applied to tackle enterovirus infections. This work analyzes registered clinical trials involving antiviral drugs to highlight the best candidates and develops filters to apply to a selection for MTDL synthesis. We explicitly stated the methods used to answer the question: which solution can fight NPEVs effectively? We note the originality and relevance of this proposal in relation to the state of the art in the enterovirus-inhibitors field. Several combinations are possible to broaden the antiviral spectrum and potency. We discuss data related to the virus and data related to each LEAD compound identified so far. Overall, this study proposes a perspective on different strategies to overcome issues identified in clinical trials and evaluate the "MTDL" potential to improve the efficacy of drugs, broaden the antiviral targets, possibly reduce the adverse effects, drug design costs and limit the selection of drug-resistant virus variants.
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Roux et al. (2024) conducted a systematic review in Non-Polio Enterovirus (NPEV) infections. Antiviral drugs and multi-target directed ligand (MTDL) synthesis was evaluated. The review identified several potential antiviral candidates for non-polio enterovirus infections and proposed the multi-target directed ligand strategy to improve efficacy and reduce drug resistance.
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