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ABC of BSAA development process. (A) Testing BSAA toxicity (left panel) and efficacy (right panel) in immortalized cell cultures and co-cultures. (B) Testing BSAA toxicity (left panel) and efficacy (right panel) in animal models. If BSAA is repositioned from another disease (i.e. its PK/PD and toxicity profiles are available for the animal model) it could bypass the safety studies. (C) Clinical trials of BSAAs. (Left panel) Pharmacokinetics (PK) and safety studies. (Right panel) Efficacy studies. If the drug is repositioned from another disease (i.e. its safety profile in man is available) it could bypass the PK and safety studies in man.

ABC of BSAA development process. (A) Testing BSAA toxicity (left panel) and efficacy (right panel) in immortalized cell cultures and co-cultures. (B) Testing BSAA toxicity (left panel) and efficacy (right panel) in animal models. If BSAA is repositioned from another disease (i.e. its PK/PD and toxicity profiles are available for the animal model) it could bypass the safety studies. (C) Clinical trials of BSAAs. (Left panel) Pharmacokinetics (PK) and safety studies. (Right panel) Efficacy studies. If the drug is repositioned from another disease (i.e. its safety profile in man is available) it could bypass the PK and safety studies in man.

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Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of gene...

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Context 1
... viability assays and cell death assays are commonly used to assess the cytotoxicity and efficacy of BSAAs ( Figure 2A). Cell viability assays include MTT, MTS, resazurin or similar assays, mitochondrial membrane potential-dependent dyes-based assays, esterase cleaved dye-based assays, ATP-ADP assays, and assays that measure glycolytic flux and oxygen consumption. ...
Context 2
... several in vivo models have been developed to test novel antiviral activities of BSAAs. These include immunocompetent and genetically or chemically immunocompromised mice, guinea pigs, hamsters, ferrets, pigs, macaques and other animals ( Figure 2B) (Alves et al., 2018;Haese et al., 2016;Louz et al., 2013;Morrison and Diamond, 2017;Taylor, 2017;Thangavel and Bouvier, 2014). PK/PD studies determine drug absorption, dosage and half-life of BSAAs. ...
Context 3
... trials are the most critical and time-consuming step of a drug candidates' journey to being approved ( Figure 2C). However, safe-in-man BSAAs make this journey relatively short, because they have been already at phase 0, I and, sometime, at IIa of clinical trials as antibacterial, antiprotozoal, anticancer, etc. agent; i.e. they have been administered at sub-therapeutic doses to healthy volunteers to ensure the drugs are not harmful to the participants. ...

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... These stem-cell derived organoid models representing fetal organ development improve our ability to mimic the toxicity and efficacy of antiviral drugs through overcoming the two-dimensionality and genetic inaccuracies of cell lines. Of note, these cellular models are also associated with some limitations, such as difficulties with culturing, batch-effect or stem cell line effect on cell culture reproducibility [176] and unintended differentiation into mixed tissue type [177]. Most importantly, such organoid models lack vascular and immune system components [178], limiting their clinical translatability. ...
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