Schistosoma mansoni carbonic anhydrase (SmCA)

Schistosoma mansoni carbonic anhydrase (SmCA) is a critical metalloenzyme expressed in the tegument of the parasitic flatworm Schistosoma mansoni, which causes intestinal schistosomiasis (MDPI, 2020; NIH, 2019). The enzyme exists in multiple forms, including a well-characterized alpha-class (SmCA) and a recently identified beta-class (SmaBCA), both of which catalyze the reversible hydration of carbon dioxide into bicarbonate and protons (NIH, 2022; TandfOnline, 2023). This catalytic activity is vital for the parasite's pH regulation, ion transport, and metabolic processes, and its suppression via RNA interference has been shown to significantly impair larval infectivity and virulence (NIH, 2019; NIH, 2022). SmCA is a validated therapeutic target, with various sulfonamide-based inhibitors and repurposed drugs like clorsulon demonstrating potent activity against the enzyme (NIH, 2022; TandfOnline, 2021). However, a major challenge in drug development is achieving high selectivity for the parasite enzyme over human carbonic anhydrase isoforms to avoid systemic side effects such as metabolic acidosis and paresthesia (NIH, 2014; TandfOnline, 2023).

Other names

SmCA1SmaBCAAlpha-carbonic anhydraseBeta-carbonic anhydraseTegumental carbonic anhydrase

Inhibition of the enzyme's catalytic activity (CO2 hydration), which disrupts pH homeostasis, ion transport, and essential metabolic pathways in the parasite.