Author:
Doan Ly Hien,Chu Li-Wei,Huang Zi-Yi,Nguyen Anh Thuc,Lee Chia-Yin,Huang Chien-Ling,Chang Yu-Fen,Hsieh Wen-Yu,Nguyen Trang Thi Huyen,Lin Chao-Hsiung,Su Chun-Li,Chuang Tsung-Hsien,Lai Jin-Mei,Wang Feng-Sheng,Yang Chia-Jui,Liu Hui-Kang,Ping Yueh-Hsin,Huang Chi-Ying F.
Abstract
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.
Funder
Ministry of Science and Technology, Taiwan
Subject
Pharmacology (medical),Pharmacology
Reference88 articles.
1. The Lung Macrophage in SARS-CoV-2 Infection: A Friend or a Foe?;Abassi;Front. Immunol.,2020
2. Remdesivir Plus Standard of Care versus Standard of Care Alone for the Treatment of Patients Admitted to Hospital with COVID-19 (DisCoVeRy): a Phase 3, Randomised, Controlled, Open-Label Trial;Ader;Lancet Infect. Dis,2021
3. Pathogenesis and Management of COVID-19;Alfarouk;JoX,2021
4. Gene Ontology: Tool for the Unification of Biology. The Gene Ontology Consortium;Ashburner;Nat. Genet.,2000
5. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19;Blanco-Melo;Cell,2020
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