Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo
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. Th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/6/1142 |
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| author | Yuexiang Li Miaomiao Liu Yunzheng Yan Zhuang Wang Qingsong Dai Xiaotong Yang Xiaojia Guo Wei Li Xingjuan Chen Ruiyuan Cao Wu Zhong |
| author_facet | Yuexiang Li Miaomiao Liu Yunzheng Yan Zhuang Wang Qingsong Dai Xiaotong Yang Xiaojia Guo Wei Li Xingjuan Chen Ruiyuan Cao Wu Zhong |
| author_sort | Yuexiang Li |
| collection | DOAJ |
| description | 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 EC<sub>50</sub> 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. |
| first_indexed | 2024-03-09T22:15:35Z |
| format | Article |
| id | doaj.art-b2425698b8a541b8b6a917ab8401e381 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:15:35Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-b2425698b8a541b8b6a917ab8401e3812023-11-23T19:24:18ZengMDPI AGViruses1999-49152022-05-01146114210.3390/v14061142Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In VivoYuexiang Li0Miaomiao Liu1Yunzheng Yan2Zhuang Wang3Qingsong Dai4Xiaotong Yang5Xiaojia Guo6Wei Li7Xingjuan Chen8Ruiyuan Cao9Wu Zhong10National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaInstitute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaNational Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, ChinaEnterovirus 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 EC<sub>50</sub> 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.https://www.mdpi.com/1999-4915/14/6/1142molnupiravirEIDD-1931enterovirusantiviral |
| spellingShingle | Yuexiang Li Miaomiao Liu Yunzheng Yan Zhuang Wang Qingsong Dai Xiaotong Yang Xiaojia Guo Wei Li Xingjuan Chen Ruiyuan Cao Wu Zhong Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo Viruses molnupiravir EIDD-1931 enterovirus antiviral |
| title | Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo |
| title_full | Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo |
| title_fullStr | Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo |
| title_full_unstemmed | Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo |
| title_short | Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo |
| title_sort | molnupiravir and its active form eidd 1931 show potent antiviral activity against enterovirus infections in vitro and in vivo |
| topic | molnupiravir EIDD-1931 enterovirus antiviral |
| url | https://www.mdpi.com/1999-4915/14/6/1142 |
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