Carbonic anhydrase inhibition by antiviral drugs in vitro and in silico
Cüneyt Türkeş
Abstract
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 ( h CA, 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 h CA I and II isoforms' active sites. The h CA 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 K I s spanning from 0.49 ± 0.05 to 3.51 ± 0.37 μM compared with the reference drug acetazolamide (AAZ, K I of 0.19 ± 0.01 μM). Moreover, h CA II, a promising target for edema, glaucoma, epilepsy, and altitude sickness, was a reasonably inhibited isoform by these agents, with K I s in the range of 0.64 ± 0.08–5.80 ± 0.64 μM compared with AAZ ( K I of 0.17 ± 0.01 μM). Both in vitro and in silico results demonstrated significant interactions between these five drugs and h CAs 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.