Abstract

Enzyme inhibition is a commonly utilized method for controlling enzymatic activity in various physiologically relevant biological systems. Herein, the selected five active antiviral drugs, abacavir, emtricitabine, lamivudine, ribavirin, and ritonavir, were assayed as inhibitors of two human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) involved in various physiological/pathological conditions. For this aim, in vitro and in silico studies were performed to gain insights into the plausible binding interactions and affinities for the antiviral drugs within hCA I and II isoforms' active sites. The hCA I, an isoform involved in some pathological conditions such as retinal or cerebral edema, was moderately inhibited by these five drugs at micromolar concentrations with KI s spanning from 0.49 ± 0.05 to 3.51 ± 0.37 μM compared with the reference drug acetazolamide (AAZ, KI of 0.19 ± 0.01 μM). Moreover, hCA II, a promising target for edema, glaucoma, epilepsy, and altitude sickness, was a reasonably inhibited isoform by these agents, with KI s in the range of 0.64 ± 0.08-5.80 ± 0.64 μM compared with AAZ (KI of 0.17 ± 0.01 μM). Both in vitro and in silico results demonstrated significant interactions between these five drugs and hCAs and that they can support therapeutic targets against the above-mentioned pathological conditions. Additionally, the results obtained will help optimize the clinical dosage regimens of these drugs and avoid drug-drug interactions unexpectedly when used in combination with other agents.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call