Molnupiravir (MOL) is a ribonucleoside prodrug for oral treatment of COVID-19. Common adverse effects of MOL are headache, diarrhea, and nausea, which may be associated with altered sodium channel function. Here, we investigated the effect of MOL on voltage-gated Na current (I) in pituitary GH cells. We show that MOL had distinct effects on transient and late I, in combination with decreased time constant in the slow component of I inactivation. The 50% inhibitory concentration (IC) values of MOL for suppressing transient and late I were 26.1 and 6.3 μM, respectively. The overall steady-state current-voltage relationship of I remained unchanged upon MOL exposure. MOL-induced alteration of I may lead to changes in physiological function through sodium channels. Apart from its effect on inhibiting RNA virus replication, MOL exerts inhibitory effects on plasmalemma I, which might constitute an additional yet crucial underlying mechanism of its pharmacological activity or adverse events.
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