Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro
IntroductionRespiratory syncytial virus (RSV) remains a major international public health concern. However, disease treatment is limited to preventive care with monoclonal antibodies and supportive care. In this study, natural products were screened to identify novel anti-RSV inhibitors.MethodsThe a...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1484245/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850243046768115712 |
|---|---|
| author | Chao Wang Chao Wang Yi-Man Huang Yi-Man Huang Jun Zhao Jun Zhao Yi-Ming Bai Yi-Ming Bai Cai-Qin Yan Cai-Qin Yan Guan-Hua Du Guan-Hua Du Li-Shu Zheng Li-Shu Zheng Ai-Lin Liu Ai-Lin Liu |
| author_facet | Chao Wang Chao Wang Yi-Man Huang Yi-Man Huang Jun Zhao Jun Zhao Yi-Ming Bai Yi-Ming Bai Cai-Qin Yan Cai-Qin Yan Guan-Hua Du Guan-Hua Du Li-Shu Zheng Li-Shu Zheng Ai-Lin Liu Ai-Lin Liu |
| author_sort | Chao Wang |
| collection | DOAJ |
| description | IntroductionRespiratory syncytial virus (RSV) remains a major international public health concern. However, disease treatment is limited to preventive care with monoclonal antibodies and supportive care. In this study, natural products were screened to identify novel anti-RSV inhibitors.MethodsThe antiviral effect of 320 compounds on RSV in HEp-2 cells was tested using a Cytopathic effect (CPE) inhibition assay. The antiviral effect of fumarprotocetraric acid (FUM) and geraniin (GE) were confirmed by Real-time reverse transcription quantitative PCR (Real-time RT-PCR), plaque reduction test, immunofluorescence assay, and Western blot analysis. Real-time PCR was used to detect inflammatory factor expression. ATP assay and JC-1 stain were used to evaluate mitochondrial protection function. The experiment of administration time was used to determine the stages in the RSV life cycle inhibited by FUM and GE. Human metapneumovirus (HMPV) and human rhinovirus (HRV) were used to evaluate the antiviral activities of other respiratory viruses of FUM and GE. Finally, Air-liquid interface human airway epithelium (ALI-HAE) cells were used to evaluate the antiviral effect and mechanism of FUM and GE to RSV.ResultsThe results showed that FUM and GE can inhibit the replication of RSV in multiple-cell models. Both compounds could dose-dependent inhibit the viral load, RSV nucleic acids level, and RSV-F protein level. Besides, FUM and GE showed good anti-inflammatory activity, mitochondrial protection, and antiviral activity to HMPV and HRV. Meanwhile, our result indicated that FUM and GE can inhibit RSV replication in ALI-HAE cells.ConclusionsFUM and GE were identified as new inhibitors of RSV infection. At the same time, FUM and GE have anti-inflammatory activity, mitochondrial protection function, and broad-spectrum antiviral activity. These results provide evidence that FUM and GE are potential candidates for the development of novel anti-RSV drugs. |
| format | Article |
| id | doaj-art-045fff3c7c44454480537cc2b8d99460 |
| institution | OA Journals |
| issn | 2235-2988 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-045fff3c7c44454480537cc2b8d994602025-08-20T02:00:07ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-12-011410.3389/fcimb.2024.14842451484245Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitroChao Wang0Chao Wang1Yi-Man Huang2Yi-Man Huang3Jun Zhao4Jun Zhao5Yi-Ming Bai6Yi-Ming Bai7Cai-Qin Yan8Cai-Qin Yan9Guan-Hua Du10Guan-Hua Du11Li-Shu Zheng12Li-Shu Zheng13Ai-Lin Liu14Ai-Lin Liu15State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, ChinaNHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, ChinaNHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Lab of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaIntroductionRespiratory syncytial virus (RSV) remains a major international public health concern. However, disease treatment is limited to preventive care with monoclonal antibodies and supportive care. In this study, natural products were screened to identify novel anti-RSV inhibitors.MethodsThe antiviral effect of 320 compounds on RSV in HEp-2 cells was tested using a Cytopathic effect (CPE) inhibition assay. The antiviral effect of fumarprotocetraric acid (FUM) and geraniin (GE) were confirmed by Real-time reverse transcription quantitative PCR (Real-time RT-PCR), plaque reduction test, immunofluorescence assay, and Western blot analysis. Real-time PCR was used to detect inflammatory factor expression. ATP assay and JC-1 stain were used to evaluate mitochondrial protection function. The experiment of administration time was used to determine the stages in the RSV life cycle inhibited by FUM and GE. Human metapneumovirus (HMPV) and human rhinovirus (HRV) were used to evaluate the antiviral activities of other respiratory viruses of FUM and GE. Finally, Air-liquid interface human airway epithelium (ALI-HAE) cells were used to evaluate the antiviral effect and mechanism of FUM and GE to RSV.ResultsThe results showed that FUM and GE can inhibit the replication of RSV in multiple-cell models. Both compounds could dose-dependent inhibit the viral load, RSV nucleic acids level, and RSV-F protein level. Besides, FUM and GE showed good anti-inflammatory activity, mitochondrial protection, and antiviral activity to HMPV and HRV. Meanwhile, our result indicated that FUM and GE can inhibit RSV replication in ALI-HAE cells.ConclusionsFUM and GE were identified as new inhibitors of RSV infection. At the same time, FUM and GE have anti-inflammatory activity, mitochondrial protection function, and broad-spectrum antiviral activity. These results provide evidence that FUM and GE are potential candidates for the development of novel anti-RSV drugs.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1484245/fullrespiratory syncytial virusfumarprotocetraric acidgeraniinantiviralnatural products |
| spellingShingle | Chao Wang Chao Wang Yi-Man Huang Yi-Man Huang Jun Zhao Jun Zhao Yi-Ming Bai Yi-Ming Bai Cai-Qin Yan Cai-Qin Yan Guan-Hua Du Guan-Hua Du Li-Shu Zheng Li-Shu Zheng Ai-Lin Liu Ai-Lin Liu Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro Frontiers in Cellular and Infection Microbiology respiratory syncytial virus fumarprotocetraric acid geraniin antiviral natural products |
| title | Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro |
| title_full | Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro |
| title_fullStr | Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro |
| title_full_unstemmed | Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro |
| title_short | Fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro |
| title_sort | fumarprotocetraric acid and geraniin were identified as novel inhibitors of human respiratory syncytial virus infection in vitro |
| topic | respiratory syncytial virus fumarprotocetraric acid geraniin antiviral natural products |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1484245/full |
| work_keys_str_mv | AT chaowang fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT chaowang fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT yimanhuang fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT yimanhuang fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT junzhao fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT junzhao fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT yimingbai fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT yimingbai fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT caiqinyan fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT caiqinyan fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT guanhuadu fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT guanhuadu fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT lishuzheng fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT lishuzheng fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT ailinliu fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro AT ailinliu fumarprotocetraricacidandgeraniinwereidentifiedasnovelinhibitorsofhumanrespiratorysyncytialvirusinfectioninvitro |