Morphothiadin (GLS4) is a potent antiviral agent that inhibits the Hepatitis B virus (HBV) replication with an IC50 value of 12nM [1]. Morphothiadin inhibits HBV replication by interfering with the assembly and disassembly of the viral nucleocapsid, suppresses the production of particles containing HBV pgRNA, and reduces the level of cccDNA[2]. Morphothiadin has been widely used to prevent HBV from infecting cells and to interfere with the formation of the viral core particles[3].
In vitro, Morphothiadin treatment for 48 hours significantly inhibited the viability of primary human hepatocytes and HepAD38 cells, with the CC50 values of 35μM and 26μM, respectively[4].
In vivo, Morphothiadin treatment via daily intragastric administration at a dose of 60mg/kg, and combined with ritonavir (40mg/kg; p.o.) for 7 days significantly reduced the HBV DNA levels in the serum of pAAV/HBV1.2 HDI mice and the expression of HBsAg in the liver, increased the expression of RIG-I in the liver tissue of the mice, and enhanced the IFN signaling pathway[5].
References:
[1] Zhou X, Gao Z, Meng J, et al. Effects of ketoconazole and rifampicin on the pharmacokinetics of GLS4, a novel anti-hepatitis B virus compound, in dogs[J]. Acta Pharmacologica Sinica, 2013, 34(11): 1420-1426.
[2] Zhang M, Gao Y, Kong F, et al. Efficacy and safety of GLS4 with entecavir vs entecavir alone in chronic hepatitis B patients: A multicenter clinical trial[J]. Journal of Infection, 2025, 90(3): 106446.
[3] Wang X Y, Wei Z M, Wu G Y, et al. In vitro inhibition of HBV replication by a novel compound, GLS4, and its efficacy against adefovir-dipivoxil-resistant HBV mutations[J]. Antiviral therapy, 2012, 17(5): 793-803.
[4] Wu G, Liu B, Zhang Y, et al. Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core particle assembly[J]. Antimicrobial agents and chemotherapy, 2013, 57(11): 5344-5354.
[5] Zhao L, Xu S, Yao S, et al. GLS4 Induces the Interferon Signaling Pathway During Hepatitis B Virus (HBV) Infection[J]. Journal of Medical Virology, 2026, 98(1): e70777.
Morphothiadin (GLS4)是一种强效抗病毒剂，可抑制乙型肝炎病毒（HBV）复制，IC50值为12nM[1]。Morphothiadin通过干扰病毒核衣壳的组装和拆卸来抑制HBV复制，抑制含有HBV pgRNA的颗粒产生，并降低cccDNA水平[2]。Morphothiadin已被广泛用于预防HBV感染细胞以及干扰病毒核心颗粒的形成[3]。
在体外，Morphothiadin处理48小时显著抑制了原代人肝细胞和HepAD38细胞的活力，CC50值分别为35μM和26μM[4]。
在体内，每日灌胃给予60mg/kg剂量的Morphothiadin，联合口服ritonavir（40mg/kg），连续7天，显著降低了pAAV/HBV1.2 HDI小鼠血清中的HBV DNA水平及肝脏中HBsAg的表达，增加了小鼠肝组织中RIG-I的表达，并增强了干扰素信号通路[5]。