Citation: Bo Yuan, Chenyun Feng, Yaofeng Yuan. Research Progress on Small-Molecule Drugs for Treating COVID-19[J]. University Chemistry, ;2023, 38(8): 85-94. doi: 10.3866/PKU.DXHX202208060 shu

Research Progress on Small-Molecule Drugs for Treating COVID-19

Bo Yuan ² ,
Chenyun Feng ^1,3,, ,
Yaofeng Yuan ^1,,

1.
College of Chemistry, Fuzhou University, Fuzhou 350108, China;
2.
National Medical Products Administration Southern Medical Economy Institute, Guangzhou 510080, China;
3.
Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, Guangdong Province, China

Corresponding author: Chenyun Feng, Yaofeng Yuan,
Received Date: 9 August 2022

The COVID-19 pandemic has caused significant losses and suffering around the world. Although the SARS-CoV-2 vaccine has largely controlled the spread of the virus, the scientific and sustainable treatment of COVID-19 patients is still necessary to truly end the pandemic. Small-molecule drugs against COVID-19 have attracted the attention of the scientific community and industry owing to their unique advantages such as a simple delivery method, relatively high output, and immune response with lower probability. Fortunately, in the last three years, some potentially effective drugs have been proposed, and have achieved good results in clinical trials. This paper briefly introduces the research progress on small-molecule drugs since 2020 to provide reference for future SARS-CoV-2 research.
- SARS-CoV-2,
- Small molecule drugs,
- RdRp,
- Azvudine,
- Paxlovid^TM
1. [1]
  Zhao, D. H.; Yao, F. F.; Wang, L. J.; Zheng, L.; Gao, Y. J.; Ye, J.; Guo, F.; Zhao, H.; Gao, R. B. Clin. Infect. Dis. 2020, 71, 756.
2. [2]
  Chan, J. F. W.; Yip, C. C. Y.; To, K. K. W.; Tang, T. H. C.; Wong, S. C. Y.; Leung, K. H.; Fung, A. Y. F.; Ng, A. C. K.; Zou, Z. J.; Tsoi, H. W.; et al. J. Clin. Microbiol. 2020, 58, e00310.
3. [3]
  Weekly epidemiological update on COVID-19.[2022-11-21].https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19——16-november-2022
4. [4]
  Douin, D. J.; Talbot, H. K.; Casey, J. D.; Mohr, N. M.; Zepeski, A.; Shapiro, N. I.; Gibbs, K. W.; Files, D. C.; Hager, D. N.; Shehu, A.; et al.BMJ-Brit. Med. J. 2022, 376, e069761.
5. [5]
  Fiolet, T.; Kherabi, Y.; MacDonald, C. J.; Ghosn, J.; Peiffer-Smadja, N. Clin. Microbiol. Infect. 2022, 28, 202.
6. [6]
7. [7]
  Barbier, A. J.; Jiang, A. Y. J.; Zhang, P.; Wooster, R.; Anderson, D. G. Nat. Biotechnol. 2022, 40, 840.
8. [8]
  CY 2021 CDER New Molecular Entity (NME) Drug & Original BLA Calendar Year Approvals As of December 31, 2021.[2022-10-09]. https://www.fda.gov/media/158152/download
9. [9]
  Emergency Use Authorization.[2022-10-09].https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs
10. [10]
  Drugs@FDA:FDA-Approved Drugs.[2022-10-09]. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=reportsSearch.process
11. [11]
  Gordon, D. E.; Jang, G. M.; Bouhaddou, M.; Xu, J. W.; Obernier, K.; White, K. M.; O'Meara, M. J.; Rezelj, V. V.; Guo, J. F. Z.; Swaney, D. L.;et al. Nature 2020, 583, 459.
12. [12]
  Ho, W. S.; Zhang, R. R.; Tan, Y. L.; Chai, C. L. L. Pharmacol. Res. 2022, 179, 106201.
13. [13]
  Saha, A.; Sharma, A. R.; Bhattacharya, M.; Sharma, G.; Lee, S. S.; Chakraborty, C. Arch. Med. Res. 2020, 51, 585.
14. [14]
  Subissi, L.; Posthuma, C. C.; Collet, A.; Zevenhoven-Dobbe, J. C.; Gorbalenya, A. E.; Decroly, E.; Snijder, E. J.; Canard, B.; Imbert, I.Proc. Natl. Acad. Sci. USA 2014, 111, E3900.
15. [15]
16. [16]
  China approves first homegrown COVID antiviral.[2022-08-01]. https://www.nature.com/articles/d41586-022-02050-x
17. [17]
  Zhang, J. L.; Li, Y. H.; Wang, L. L.; Liu, H. Q.; Lu, S. Y.; Liu, Y.; Li, K.; Liu, B.; Li, S. Y.; Shao, F. M.; et al. Signal Transduct. Target. Ther.2021, 6 (1), 414.
18. [18]
  Chang, J. B. Acc. Chem. Res. 2022,55, 565.
19. [19]
  Yu, B.; Chang, J. B. Signal Transduct. Target. Ther. 2020,5, 236.
20. [20]
  Ren, Z. G.; Luo, H.; Yu, Z. J.; Song, J. C.; Liang, L.; Wang, L.; Wang, H. Y.; Cui, G. Y.; Liu, Y.; Wang, J.; et al. Adv. Sci. 2020,7, 2001435.
21. [21]
  Tang, W.; Cao, Z. J.; Han, M. F.; Wang, Z. Y.; Chen, J. W.; Sun, W. J.; Wu, Y. J.; Xiao, W.; Liu, S. Y.; Chen, E. Z.; et al. BMJ-Brit. Med. J. 2020, 369, m1849.
22. [22]
23. [23]
  Khiali, S.; Khani, E.; Rouy, S. B.; Rouy, S. B.; Entezari-Maleki, T. Future Microbiol. 2022, 17, 377.
24. [24]
  Kabinger, F.; Stiller, C.; Schmitzoval, J.; Dienemann, C.; Kokic, G.; Hillen, H. S.; Hobartner, C.; Cramer, P. Nat. Struct. Mol. Biol. 2021,28, 740.
25. [25]
  Painter, W. P.; Holman, W.; Bush, J. A.; Almazedi, F.; Malik, H.; Eraut, N.; Morin, M. J.; Szewczyk, L. J.; Painter, G. R. Antimicrob. Agents Chemother. 2021, 65, e02428-20.
26. [26]
  Fischer, W. A.; Eron, J. J.; Holman, W.; Cohen, M. S.; Fang, L.; Szewczyk, L. J.; Sheahan, T. P.; Baric, R.; Mollan, K. R.; Wolfe, C. R.; et al.Sci. Transl. Med. 2022, 14, eabl7430.
27. [27]
  Thorlund, K.; Sheldrick, K.; Mills, E. N. Engl. J. Med. 2022,386, e32.
28. [28]
  Beigel, J. H.; Tomashek, K. M.; Dodd, L. E.; Mehta, A. K.; Zingman, B. S.; Kalil, A. C.; Hohmann, E.; Chu, H. Y.; Luetkemeyer, A.; Kline, S.;et al. N. Engl. J. Med. 2020, 383, 1813.
29. [29]
  Ader, F.; Bouscambert-Duchamp, M.; Hites, M.; Peiffer-Smadja, N.; Mentre, F.; Burdet, C.; DisCoVeRy Study Group Lancet Infect. Dis. 2022,22, 764.
30. [30]
  Hammond, J.; Leister-Tebbe, H.; Gardner, A.; Abreu, P.; Bao, W. H.; Wisemandle, W.; Baniecki, M.; Hendrick, V. M.; Damle, B.; Simon-Campos, A.; et al. N. Engl. J. Med. 2022,386, 1397.
31. [31]
  Lee, J. T.; Yang, Q. Y.; Gribenko, A.; Perrin, B. S.; Zhu, Y. A.; Cardin, R.; Liberator, P. A.; Anderson, A. S.; Hao, L. MBIO 2022, 7, 00867.
32. [32]
  Mahdi, M.; Motyan, J. A.; Szojka, Z. I.; Golda, M.; Miczi, M. Virol. J. 2020, 17, 190.
33. [33]
  Zwart, D. Trop. Geogr. Med. 2003, 914, 340.
34. [34]
  Vohra, M.; Sharma, A. R.; Satyamoorthy, K.; Rai, P. S. Pers. Med. 2021, 18, 389.
35. [35]
  Mahmudpour, M.; Roozbeh, J.; Keshavarz, M.; Farrokhi, S.; Nabipour, I. l. Cyokine 2020, 133, 155151.
36. [36]
  Sinha, S.; Rosin, N. L.; Arora, R.; Labit, E.; Jaffer, A.; Cao, L. L.; Farias, R.; Nguyen, A. P.; de Almeida, L. G. N.; Dufour, A.; et al. Nat. Med. 2022, 28, 201.
37. [37]
  Giles, A. J.; Hutchinson, M.; Sonnemann, H. M.; Jung, J.; Fecci, P. E.; Ratnam, N. M.; Zhang, W.; Song, H.; Bailey, R.; Davis, D.; et al.J. Immunother. Cancer 2018, 6, 51.
38. [38]
  Horby, P.; Lim, W. S.; Emberson, J. R.; Mafham, M.; Bell, J. L.; Linsell, L.; Staplin, N.; Brightling, C.; Ustianowski, A.; Elmahi, E.; et al.N. Engl. J. Med. 2021, 384, 693.
39. [39]
  Malkawi, A. K.; Alzoubi, K. H.; Jacob, M.; Matic, G.; Ali, A.; Al Faraj, A.; Almuhanna, F.; Dasouki, M.; Rahman, A. M. A. Front. Pharmacol. 2018, 9, 46.
40. [40]
  Mogul, A.; Corsi, K.; McAuliffe, L. Ann. Pharmacother. 2019,53, 947.
41. [41]
  Jorgensen, S. C. J.; Tse, C. L. Y.; Burry, L. Pharmacotherapy 2020, 40, 843.
42. [42]
  Kulkarni, S.; Fisk, M.; Kostapanos, M.; Banham-Hall, E.; Bond, S.; Hernan-Sancho, E.; Norton, S.; Cheriyan, J.; Cope, A.; Galloway, J.; et al. Trials 2020, 21, 46.
43. [43]
  Kalil, A. C.; Patterson, T. F.; Mehta, A. K.; Tomashek, K. M.; Wolfe, C. R.; Ghazaryan, V.; Marconi, V. C.; Ruiz-Palacios, G. M.; Hsieh, L.;Kline, S.; et al. N. Engl. J. Med. 2021, 384, 795.
44. [44]
  Rodriguez-Garcia, J. L.; Sanchez-Nievas, G.; Arevalo-Serrano, J.; Garcia-Gomez, C.; Jimenez-Vizuete, J. M.; Martinez-Alfaro, E. Rheumatology 2021, 60, 399.
45. [45]
  Kramer, A.; Prinz, C.; Fichtner, F.; Fischer, A. L.; Thieme, V.; Grundeis, F.; Spagl, M.; Seeber, C.; Piechotta, V.; Metzendorf, M. I.; et al.Cochrane Db. Syst. Rev. 2022, 6, CD015209.
46. [46]
  Fu, Z.; Huang, B.; Tang, J.; Liu, S.; Liu, M.; Ye, Y.; Liu, Z.; Xiong, Y.; Zhu, W.; Cao, D.; et al. Nat. Commun. 2021, 12, 488.
47. [47]
  Osipiuk, J.; Azizi, S. A.; Dvorkin, S.; Endres, M.; Jedrzejczak, R.; Jones, K. A.; Kang, S.; Kathayat, R. S.; Kim, Y.; Lisnyak, V. G.; et al.Nat. Commun. 2021, 12, 743.
48. [48]
  Richardson, P.; Griffin, I.; Tucker, C.; Smith, D.; Oechsle, O.; Phelan, A.; Rawling, M.; Savory, E.; Stebbing, J. Lancet 2020, 395 (10223), e30.
1. [1]
  Chunyu Yan , Qinglong Qiao , Wei Zhou , Xuelian Zhou , Yonghui Chen , Lu Miao , Zhaochao Xu . FRET-based in vitro assay for rapid detecting of SARS-CoV-2 entry inhibitors. Chinese Chemical Letters, 2025, 36(5): 110258-. doi: 10.1016/j.cclet.2024.110258
2. [2]
  Zheqi Wang , Yawen Lin , Shunliu Deng , Huijun Zhang , Jinmei Zhou . Antiviral Strategies: A Brief Review of the Development History of Small Molecule Antiviral Drugs. University Chemistry, 2024, 39(9): 85-93. doi: 10.12461/PKU.DXHX202403108
3. [3]
  Yang Li , Ning Sheng , Kun Wang , Yuhuan Li , Jiandong Jiang , Jinlan Zhang . Azvudine alleviates SARS-CoV-2-induced inflammation by targeting myeloperoxidase in NETosis. Chinese Chemical Letters, 2025, 36(5): 110238-. doi: 10.1016/j.cclet.2024.110238
4. [4]
  Yulong Shi , Fenbei Chen , Mengyuan Wu , Xin Zhang , Runze Meng , Kun Wang , Yan Wang , Yuheng Mei , Qionglu Duan , Yinghong Li , Rongmei Gao , Yuhuan Li , Hongbin Deng , Jiandong Jiang , Yanxiang Wang , Danqing Song . Chemical construction and anti-HCoV-OC43 evaluation of novel 10,12-disubstituted aloperine derivatives as dual cofactor inhibitors of TMPRSS2 and SR-B1. Chinese Chemical Letters, 2024, 35(5): 108792-. doi: 10.1016/j.cclet.2023.108792
5. [5]
  Zhichao Zhou , Fuqian Chen , Xiaotong Xia , Dong Ye , Rong Zhou , Lei Li , Tao Deng , Zhenhua Ding , Fang Liu . Developing a fluorescence substrate for HRP-based diagnostic assays with superiorities over the commercial ADHP. Chinese Chemical Letters, 2024, 35(6): 108970-. doi: 10.1016/j.cclet.2023.108970
6. [6]
  Yunxin Li , Jinghui Zhang , Jisen Chen , Feng Zhu , Zhiqiang Liu , Peng Bao , Wei Shen , Sheng Tang . Detection of SARS-CoV-2 based on artificial intelligence-assisted smartphone: A review. Chinese Chemical Letters, 2024, 35(7): 109220-. doi: 10.1016/j.cclet.2023.109220
7. [7]
  Gengchen Guo , Tianyu Zhao , Ruichang Sun , Mingzhe Song , Hongyu Liu , Sen Wang , Jingwen Li , Jingbin Zeng . Au-Fe₃O₄ dumbbell-like nanoparticles based lateral flow immunoassay for colorimetric and photothermal dual-mode detection of SARS-CoV-2 spike protein. Chinese Chemical Letters, 2024, 35(6): 109198-. doi: 10.1016/j.cclet.2023.109198
8. [8]
  Wenyan Dan , Weijie Li , Xiaogang Wang . The Technical Analysis of Visual Software ShelXle for Refinement of Small Molecular Crystal Structure. University Chemistry, 2024, 39(3): 63-69. doi: 10.3866/PKU.DXHX202302060
9. [9]
  Zhifang SU , Zongjie GUAN , Yu FANG . Process of electrocatalytic synthesis of small molecule substances by porous framework materials. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2373-2395. doi: 10.11862/CJIC.20240290
10. [10]
  Dan Liu . 可见光-有机小分子协同催化的不对称自由基反应研究进展. University Chemistry, 2025, 40(6): 118-128. doi: 10.12461/PKU.DXHX202408101
11. [11]
  Ziheng Zhuang , Xiao Xu , Kin Shing Chan . Superdrugs for Superbugs. University Chemistry, 2024, 39(9): 128-133. doi: 10.3866/PKU.DXHX202309040
12. [12]
  Yong Shu , Xing Chen , Sai Duan , Rongzhen Liao . How to Determine the Equilibrium Bond Distance of Homonuclear Diatomic Molecules: A Case Study of H₂. University Chemistry, 2024, 39(7): 386-393. doi: 10.3866/PKU.DXHX202310102
13. [13]
  Xin MA , Ya SUN , Na SUN , Qian KANG , Jiajia ZHANG , Ruitao ZHU , Xiaoli GAO . A Tb₂ complex based on polydentate Schiff base: Crystal structure, fluorescence properties, and biological activity. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1347-1356. doi: 10.11862/CJIC.20230357
14. [14]
  Runze Xu , Rui Liu . U-Pb Dating in the Age of Dinosaurs. University Chemistry, 2024, 39(9): 243-247. doi: 10.12461/PKU.DXHX202404083
15. [15]
  Xuanzhu Huo , Yixi Liu , Qiyu Wu , Zhiqiang Dong , Chanzi Ruan , Yanping Ren . Integrated Experiment of “Electrolytic Preparation of Cu₂O and Gasometric Determination of Avogadro’s Constant: Implementation, Results, and Discussion: A Micro-Experiment Recommended for Freshmen in Higher Education at Various Levels Across the Nation. University Chemistry, 2024, 39(3): 302-307. doi: 10.3866/PKU.DXHX202308095
16. [16]
  Yifeng Xu , Jiquan Liu , Bin Cui , Yan Li , Gang Xie , Ying Yang . “Xiao Li’s School Adventures: The Working Principles and Safety Risks of Lithium-ion Batteries”. University Chemistry, 2024, 39(9): 259-265. doi: 10.12461/PKU.DXHX202404009
17. [17]
  Peng Zhan . Practice and Reflection in Training Medicinal Chemistry Graduate Students. University Chemistry, 2024, 39(6): 112-121. doi: 10.3866/PKU.DXHX202402022
18. [18]
  Zhibei Qu , Changxin Wang , Lei Li , Jiaze Li , Jun Zhang . Organoid-on-a-Chip for Drug Screening and the Inherent Biochemistry Principles. University Chemistry, 2024, 39(7): 278-286. doi: 10.3866/PKU.DXHX202311039
19. [19]
  Jiahao Zeng , Hui Chao . 诱导程序性细胞死亡的金属抗肿瘤药物研究. University Chemistry, 2025, 40(6): 145-159. doi: 10.12461/PKU.DXHX202406019
20. [20]
  Zhilian Liu , Wengui Wang , Hongxiao Yang , Yu Cui , Shoufeng Wang . Ideological and Political Education Design for the Synthesis of Irinotecan Drug Intermediate 7-Ethyl Camptothecin. University Chemistry, 2024, 39(2): 89-93. doi: 10.3866/PKU.DXHX202306012

Get Citation

PDF

XML

Metrics

PDF Downloads(13)
Abstract views(1516)
HTML views(115)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142