Harnessing the Potential of Enzymes as Inhaled Therapeutics in Respiratory Tract Diseases: A Review of the Literature

Abstract

Respiratory tract diseases (RTDs) are a global cause of mortality and affect patient well-being and quality of life. Specifically, there is a high unmet need concerning respiratory tract infections (RTIs) due to limitations of vaccines and increased antibiotic resistance. Enzyme therapeutics, and in particular plant-based enzymes, represent an underutilised resource in drug development warranting further attention. This literature review aims to summarise the current state of enzyme therapeutics in medical applications, with a focus on their potential to improve outcomes in RTDs, including RTIs. We used a narrative review approach, searching PubMed and clinicaltrials.gov with search terms including: enzyme therapeutics, enzyme therapy, inhaled therapeutics, botanical enzyme therapeutics, plant enzymes, and herbal extracts. Here, we discuss the advantages and challenges of enzyme therapeutics in the setting of RTDs and identify and describe several enzyme therapeutics currently used in the respiratory field. In addition, the review includes recent developments concerning enzyme therapies and plant enzymes in (pre-)clinical stages. The global coronavirus disease 2019 (COVID-19) pandemic has sparked development of several promising new enzyme therapeutics for use in the respiratory setting, and therefore, it is timely to provide a summary of recent developments, particularly as these therapeutics may also prove beneficial in other RTDs.

Non‐seed plants are emerging gene sources for agriculture and insect control proteins

“…These include famous examples sourced from seed plants for medicinal properties, such as atropine, caffeine, cocaine, codeine, digitalin, L‐dopa, ephedrine, nicotine, quinine, salicin, strychnine, and taxol, among others. Proteins with medicinal uses are comparatively rare, the mucolytic activity of papain proteolytic enzymes derived from papaya is one example (Vanderstocken et al., 2022). In conclusion, the available examples of safe oral medicinal uses of non‐seed plants, and associated toxicity due to super‐optimal dosage or exposure, largely point to metabolites, not to proteins directly, and not to non‐enzymatic proteins such as the insecticidal active protein classes described above.…”