The Bis(1,2,3,4-tetrahydroisoquinoline) Alkaloids Cepharanthine and Berbamine Are Ligands of SK Channels.

Cepharanthine, a multitarget alkaloid which has recently been shown to be effective against SARS-Cov-2, and berbamine, an alkaloid characterized as a calcium channel blocker, both share key structural elements with known small conductance calcium-activated potassium (SK) channel blockers. These structural similarities led us to evaluate their affinity for SK channels. Therefore, we performed binding on SK2 and SK3 subtypes and highlighted micromolar to sub-micromolar affinities. Respectively, the K values on SK2 and SK3 are 1,318 μM and 1,091 μM for cepharanthine and 0,284 μM and 0,679 μM for berbamine. These newfound affinities correspond to the concentrations at which the alkaloids are found to be active against several pathologies. As SK interactions occur at the same levels as their therapeutic effects, there is a strong incentive to further investigate whether SK channels are involved in their pharmaceutical potency.