Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo

被引:17
作者
Li, Yuexiang [1 ]
Liu, Miaomiao [1 ]
Yan, Yunzheng [1 ]
Wang, Zhuang [1 ,2 ]
Dai, Qingsong [1 ]
Yang, Xiaotong [1 ]
Guo, Xiaojia [1 ]
Li, Wei [1 ]
Chen, Xingjuan [2 ]
Cao, Ruiyuan [1 ]
Zhong, Wu [1 ]
机构
[1] Beijing Inst Pharmacol & Toxicol, Natl Engn Res Ctr Emergency Drug, Beijing 100850, Peoples R China
[2] Northwestern Polytech Univ, Inst Med Res, Xian 710072, Peoples R China
来源
VIRUSES-BASEL | 2022年 / 14卷 / 06期
关键词
molnupiravir; EIDD-1931; enterovirus; antiviral; 71; VACCINE; MOUTH-DISEASE; REPLICATION; ANALOG; INHIBITION; EFFICACY; SPECTRUM; SAFETY; SYSTEM; CHINA;
D O I
10.3390/v14061142
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Enterovirus infections can cause hand, foot, and mouth disease (HFDM), aseptic meningitis, encephalitis, myocarditis, and acute flaccid myelitis, leading to death of infants and young children. However, no specific antiviral drug is currently available for the treatment of this type of infection. The Unites States and United Kingdom health authorities recently approved a new antiviral drug, molnupiravir, for the treatment of COVID-19. In this study, we reported that molnupiravir (EIDD-2801) and its active form, EIDD-1931, have broad-spectrum anti-enterovirus potential. Our data showed that EIDD-1931 could significantly reduce the production of EV-A71 progeny virus and the expression of EV-A71 viral protein at non-cytotoxic concentrations. The results of the time-of-addition assay suggest that EIDD-1931 acts at the post-entry step, which is in accordance with its antiviral mechanism. The intraperitoneal administration of EIDD-1931 and EIDD-2801 protected 1-day-old ICR suckling mice from lethal EV-A71 challenge by reducing the viral load in various tissues of the infected mice. The pharmacokinetics analysis indicated that the plasma drug concentration overwhelmed the EC50 for enteroviruses, suggesting the clinical potential of molnupiravir against enteroviruses. Thus, molnupiravir along with its active form, EIDD-1931, may be a promising drug candidate against enterovirus infections.
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页数:12
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