Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants
文献类型：期刊论文
| 作者 | Xing, Jing10; Shankar, Rama10; Ko, Meehyun9; Zhang, Keke8; Zhang, Sulin8; Drelich, Aleksandra6,7; Paithankar, Shreya10; Chekalin, Eugene10; Chua, Mei-Sze5; Rajasekaran, Surender4,10 |
| 刊名 | ISCIENCE
 |
| 出版日期 | 2022-10-21 |
| 卷号 | 25期号:10页码:28 |
| DOI | 10.1016/j.isci.2022.105068 |
| 通讯作者 | Kim, Seungtaek(seungtaek.kim@ip-korea.org) ; Chen, Bin(chenbi12@msu.edu) |
| 英文摘要 | The molecular manifestations of host cells responding to SARS-CoV-2 and its evolving variants of infection are vastly different across the studied models and conditions, imposing challenges for host-based antiviral drug discovery. Based on the postulation that antiviral drugs tend to reverse the global host gene expression induced by viral infection, we retrospectively evaluated hundreds of signatures derived from 1,700 published host transcriptomic profiles of SARS/MERS/SARS-CoV-2 infection using an iterative data-driven approach. A few of these signatures could be reversed by known anti-SARS-CoV-2 inhibitors, suggesting the potential of extrapolating the biology for new variant research. We discovered IMD-0354 as a promising candidate to reverse the signatures globally with nanomolar IC50 against SARS-CoV-2 and its five variants. IMD-0354 stimulated type I interferon antiviral response, inhibited viral entry, and down-regulated hijacked proteins. This study demonstrates that the conserved coronavirus signatures and the transcriptomic reversal approach that leverages polypharmacological effects could guide new variant therapeutic discovery. |
| WOS关键词 | CONNECTIVITY MAP |
| 资助项目 | MSU Global Impact Initiative[R01GM134307] ; MSU Global Impact Initiative[K01 ES028047] ; National Culture Collection for Pathogens of Korea[NCCP43326] ; National Culture Collection for Pathogens of Korea[NCCP43381] ; National Culture Collection for Pathogens of Korea[NCCP43382] ; National Culture Collection for Pathogens of Korea[NCCP43390] ; National Culture Collection for Pathogens of Korea[NCCP43388] ; National Culture Collection for Pathogens of Korea[NCCP43389] ; National Research Foundation of Korea (NRF) - Korean government (MSIT)[NRF-2017M3A9G6068245] ; National Research Foundation of Korea (NRF) - Korean government (MSIT)[NRF-2020M3E9A1041756] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | CELL PRESS |
| WOS记录号 | WOS:000860995000004 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302661]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Kim, Seungtaek; Chen, Bin |
| 作者单位 | 1.Michigan State Univ, Dept Comp Sci & Engn, E Lansing, MI 48824 USA 2.Michigan State Univ, Dept Pharmacol & Toxicol, Grand Rapids, MI 49503 USA 3.Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA 4.Helen DeVos Childrens Hosp, Grand Rapids, MI 49503 USA 5.Stanford Univ, Dept Surg, Sch Med, Palo Alto, CA USA 6.Univ Texas Med Branch, Dept Immunol, Galveston, TX 77555 USA 7.Univ Texas Med Branch, Dept Microbiol, Galveston, TX 77555 USA 8.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China 9.Inst Pasteur Korea, Zoonot Virus Lab, Seongnam Si 13488, Gyeonggi Do, South Korea 10.Michigan State Univ, Dept Pediat & Human Dev, Grand Rapids, MI 49503 USA |
| 推荐引用方式 GB/T 7714 | Xing, Jing,Shankar, Rama,Ko, Meehyun,et al. Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants[J]. ISCIENCE,2022,25(10):28. |
| APA | Xing, Jing.,Shankar, Rama.,Ko, Meehyun.,Zhang, Keke.,Zhang, Sulin.,...&Chen, Bin.(2022).Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants.ISCIENCE,25(10),28. |
| MLA | Xing, Jing,et al."Deciphering COVID-19 host transcriptomic complexity and variations for therapeutic discovery against new variants".ISCIENCE 25.10(2022):28. |
入库方式： OAI收割
来源：上海药物研究所
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