Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2
Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.905197/full |
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| author | Ly Hien Doan Ly Hien Doan Li-Wei Chu Zi-Yi Huang Zi-Yi Huang Anh Thuc Nguyen Anh Thuc Nguyen Chia-Yin Lee Chia-Yin Lee Chien-Ling Huang Yu-Fen Chang Wen-Yu Hsieh Trang Thi Huyen Nguyen Chao-Hsiung Lin Chao-Hsiung Lin Chao-Hsiung Lin Chun-Li Su Tsung-Hsien Chuang Jin-Mei Lai Feng-Sheng Wang Chia-Jui Yang Hui-Kang Liu Hui-Kang Liu Hui-Kang Liu Yueh-Hsin Ping Yueh-Hsin Ping Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang |
| author_facet | Ly Hien Doan Ly Hien Doan Li-Wei Chu Zi-Yi Huang Zi-Yi Huang Anh Thuc Nguyen Anh Thuc Nguyen Chia-Yin Lee Chia-Yin Lee Chien-Ling Huang Yu-Fen Chang Wen-Yu Hsieh Trang Thi Huyen Nguyen Chao-Hsiung Lin Chao-Hsiung Lin Chao-Hsiung Lin Chun-Li Su Tsung-Hsien Chuang Jin-Mei Lai Feng-Sheng Wang Chia-Jui Yang Hui-Kang Liu Hui-Kang Liu Hui-Kang Liu Yueh-Hsin Ping Yueh-Hsin Ping Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang |
| author_sort | Ly Hien Doan |
| collection | DOAJ |
| description | Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading. |
| first_indexed | 2024-12-12T11:34:59Z |
| format | Article |
| id | doaj.art-de3c1b389c05418dbf5a97ca9d5e688d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T11:34:59Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-de3c1b389c05418dbf5a97ca9d5e688d2022-12-22T00:25:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.905197905197Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2Ly Hien Doan0Ly Hien Doan1Li-Wei Chu2Zi-Yi Huang3Zi-Yi Huang4Anh Thuc Nguyen5Anh Thuc Nguyen6Chia-Yin Lee7Chia-Yin Lee8Chien-Ling Huang9Yu-Fen Chang10Wen-Yu Hsieh11Trang Thi Huyen Nguyen12Chao-Hsiung Lin13Chao-Hsiung Lin14Chao-Hsiung Lin15Chun-Li Su16Tsung-Hsien Chuang17Jin-Mei Lai18Feng-Sheng Wang19Chia-Jui Yang20Hui-Kang Liu21Hui-Kang Liu22Hui-Kang Liu23Yueh-Hsin Ping24Yueh-Hsin Ping25Chi-Ying F. Huang26Chi-Ying F. Huang27Chi-Ying F. Huang28Chi-Ying F. Huang29Chi-Ying F. Huang30Chi-Ying F. Huang31Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, VietnamDepartment and Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanProgram in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanASUS Intelligent Cloud Services, Taipei, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanTaiwan National Graduate Program in Molecular Medicine, Academia Sinica, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Taiwan;Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanLumiSTAR Biotechnology, Inc., Taipei, TaiwanDivision of Basic Chinese Medicine, National Research Institute of Chinese Medicine (NRICM), Ministry of Health and Welfare, Taipei, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan0Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan1Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan2Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei, TaiwanImmunology Research Center, National Health Research Institutes, Zhunan, Taiwan;3Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan4Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan5Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, TaiwanDivision of Basic Chinese Medicine, National Research Institute of Chinese Medicine (NRICM), Ministry of Health and Welfare, Taipei, Taiwan6Ph.D. Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan7Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, TaiwanDepartment and Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan8Institute of Biophotonics, College of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, TaiwanInstitute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanProgram in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanTaiwan National Graduate Program in Molecular Medicine, Academia Sinica, National Yang Ming Chiao Tung University, Taipei, Taiwan9Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan0Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan1Department of Biochemistry, School of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCoronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.https://www.frontiersin.org/articles/10.3389/fphar.2022.905197/fullCOVID-19SARS-CoV-2 variantsOmicron variant (SARS-CoV-2)Delta variant (B.1.617.2)ACE2 (angiotensin-converting enzyme 2)miRNA |
| spellingShingle | Ly Hien Doan Ly Hien Doan Li-Wei Chu Zi-Yi Huang Zi-Yi Huang Anh Thuc Nguyen Anh Thuc Nguyen Chia-Yin Lee Chia-Yin Lee Chien-Ling Huang Yu-Fen Chang Wen-Yu Hsieh Trang Thi Huyen Nguyen Chao-Hsiung Lin Chao-Hsiung Lin Chao-Hsiung Lin Chun-Li Su Tsung-Hsien Chuang Jin-Mei Lai Feng-Sheng Wang Chia-Jui Yang Hui-Kang Liu Hui-Kang Liu Hui-Kang Liu Yueh-Hsin Ping Yueh-Hsin Ping Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Chi-Ying F. Huang Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 Frontiers in Pharmacology COVID-19 SARS-CoV-2 variants Omicron variant (SARS-CoV-2) Delta variant (B.1.617.2) ACE2 (angiotensin-converting enzyme 2) miRNA |
| title | Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 |
| title_full | Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 |
| title_fullStr | Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 |
| title_full_unstemmed | Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 |
| title_short | Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2 |
| title_sort | virofree an herbal medicine based formula interrupts the viral infection of delta and omicron variants of sars cov 2 |
| topic | COVID-19 SARS-CoV-2 variants Omicron variant (SARS-CoV-2) Delta variant (B.1.617.2) ACE2 (angiotensin-converting enzyme 2) miRNA |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.905197/full |
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