Efficacy and risks: the other side of One Health drugs

From the design of safer human and veterinary drugs to the monitoring and remediation of environmental contaminants, chemistry is uniquely positioned to provide innovative tools and knowledge. Existing drugs for human and animal parasitic infectious diseases (especially vector-borne parasitic diseases) are often scarce, have limited efficacy, and may present toxicity issues. The misuse and overuse of antimicrobials in both human and veterinary medicine drive antimicrobial drug resistance (AMR), a major global health threat [1,2]. The One Health mandates coordinated efforts to promote responsible use and preserve the efficacy of critically important antimicrobials for human use. Chemistry is of paramount importance as the use and disposal of pharmaceuticals result in their residues (Active Pharmaceutical Ingredients, API, and metabolites) entering the environment (water, soil, biota) and contaminating it. The goal for these therapeutics is to focus on the chemistry, improve their structural diversity in a controlled manner, and plan a development under the ecotoxicology framework where chemistry is highly determinant in driving safer outcomes. Therefore, prevention approaches are necessary. Our work in a collaborative network of scientists from different chemical and environmental science disciplines show how tailored greener approaches may provide safer structural templates that can be developed into drugs. Safer scaffolds today may correspond to safer drugs tomorrow. This presentation showcases our recent work aimed at transforming drug discovery by integrating ecotoxicological principles right in the early stages of drug discovery process. Our aim is to introduce novel approaches, including cleaner scaffold selection, where a machine learning-driven approach generates environmentally friendlier starting compounds for drug development. A second topic shows how ecotox-clean target identification can be achieved thought an integrated multi-omic approach (MS based Proteomics and transcriptomics) in Leishmania infantum drug resistant strains [3]. In this effort, the phylogenomic SeqAPASS tool was adopted to confirm specie-specific and ecotoxicologically free parasite protein target(s) [4]. Despite the experimental translation to effective demonstration of the efficacy of the tool promoted is ongoing, a step forward has been performed and new principles consolidated.