Molnupiravir, a ribonucleoside antiviral prodrug against SARS-CoV-2, alters the voltage-gated sodium current and causes adverse events

被引:2
|
作者
Shiau, Ai-Li [1 ,2 ]
Lee, Kuan-Hsien [3 ]
Cho, Hsin-Yen [4 ]
Chuang, Tzu-Hsien [4 ]
Yu, Meng-Cheng [4 ]
Wu, Chao-Liang [1 ,5 ]
Wu, Sheng-Nan [4 ,6 ]
机构
[1] Ditmanson Med Fdn, Chia Yi Christian Hosp, Chiayi 60002, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan
[3] Chia Yi Christian Hosp, Ditmanson Med Fdn, Dept Emergency Med, Chiayi 60002, Taiwan
[4] Natl Cheng Kung Univ, Coll Med, Dept Physiol, Tainan 70101, Taiwan
[5] Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 70101, Taiwan
[6] Natl Sun Yat Sen Univ, Coll Med, Sch Med, Kaohsiung 80424, Taiwan
关键词
Voltage -gated Na plus current; Late Na plus current; Resurgent Na plus current; Sodium channel; Antiviral drug; SARS-CoV-2; COVID-19; Adverse effect; Molnupiravir (EIDD-2801 MK-4482); TUMOR GH(3) CELLS; POTASSIUM CHANNELS; ION CURRENTS; RESURGENT; PERSISTENT; INACTIVATION; TEFLUTHRIN; NG108-15;
D O I
10.1016/j.virol.2023.109865
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 (INa) in pituitary GH3 cells. We show that MOL had distinct effects on transient and late INa, in combination with decreased time constant in the slow component of INa inactivation. The 50% inhibitory concentration (IC50) values of MOL for suppressing transient and late INa were 26.1 and 6.3 & mu;M, respectively. The overall steady-state current-voltage relationship of INa remained un-changed upon MOL exposure. MOL-induced alteration of INa 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 INa, which might constitute an additional yet crucial underlying mechanism of its pharmacological activity or adverse events.
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页数:14
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