上市小分子抗病毒药物研究进展

doi:10.3866/PKU.DXHX202212054

Abstract

Abstract:

The COVID-19, AIDS, influenza, and other infectious viral diseases have a significant impact on human health, and new antiviral drugs are continuously emerging to combat these diseases. Herein, aiming at anti-SARS-CoV-2, anti-HIV, and anti-influenza virus, the latest research progress of small-molecule drugs is reported in this paper. The discovery process, mechanism of action, synthesis process, and structure–activity relationship research of each drug are systematically expounded to promote antiviral drug research and development.

Key words: Antiviral drugs, CIOVID-19, AIDS, Influenza, Small molecule drugs

Shengzhi Xue, Jinlong Bi, Xin-Ping Hui, Quan-Xiang Wu. Research Progress of Commercial Small-Molecule Antiviral Drugs[J].University Chemistry, 2023, 38(12): 91-105.

Figures/Tables 26

References 35

1	Beck H. ; Härter M. ; Haß B. ; Schmeck C. ; Baerfacker L. Drug Discov. Today 2022, 27, 1560. doi: 10.1016/j.drudis.2022.02.015
2	Brown D. G. ; Wobst H. J.J. Med. Chem. 2021, 64, 2312. doi: 10.1021/acs.jmedchem.0c01516
3	Imran M. ; Arora M. K. ; Asdaq S. M. B. ; Khan S. A. ; Alaqel S. I. ; Alshammari M. K. ; Alshehri M. M. ; Alshrari A. S. ; Ali A. M. ; Al-shammeri A. M. ; et al Molecules 2021, 26, 5795. doi: 10.3390/molecules26195795
4	Tao K. ; Tzou P. L. ; Janin N. ; Hector B. ; Prasanna J. ; Robert W. S. Clin. Microbiol. Rev. 2021, 34, e00109- 21.
5	Kabinger F. ; Stiller C. ; Schmitzová J. ; Dienemann C. ; Kokic G. ; Hillen H. S. ; Höbartner C. ; Cramer P. Nat. Struct. Mol. Biol. 2021, 28, 740. doi: 10.1038/s41594-021-00651-0
6	陈剑, 余长泉, 陈晨. 一种4-肟-5’-(2-甲基丙酰基)尿苷的制备: 中国, CN112552288A[P]. 2021-03-26.
7	Hoffman R. L. ; Kania R. S. ; Brothers M. A. ; Davies J. F. ; Ferre R. A. ; Gajiwala K. S. ; He M. ; Hogan R. J. ; Kozminski K. ; Li L. Y. ; et al J. Med. Chem. 2020, 63, 12725. doi: 10.1021/acs.jmedchem.0c01063
8	Reina J. ; Iglesias C. Rev. Esp. Quimioter. 2022, 35, 236. doi: 10.37201/req/002.2022
9	Dinda B. ; Dinda M. ; Dinda S. ; Chakraborty M. Eur. J. Med. Chem. Rep. 2022, 6, 100079.
10	Joyce R. P. ; Hu V. W. ; Wang J.Med. Chem. Res. 2022, 31, 1637. doi: 10.1007/s00044-022-02951-6
11	Owen D. R. ; Allerton C. M. N. ; Anderson A. S. ; Aschenbrenner L. ; Avery M. ; Berritt S. ; Boras B. ; Cardin R. D. ; Carlo A. ; Coffman K. J. ; et al Science 2021, 374, 1586. doi: 10.1126/science.abl4784
12	Cho A. ; Saunders O. L. ; Butler T. ; Zhang L. ; Xu J. ; Vela J. E. ; Feng J. Y. ; Ray A. S. ; Kim C. U. Bioorg. Med. Chem. Lett. 2012, 22, 2705. doi: 10.1016/j.bmcl.2012.02.105
13	Cho A. ; Zhang L. ; Xu J. ; Lee R. ; Butler T. ; Metobo S. ; Aktoudianakis V. ; Lew W. ; Ye H. ; Clarke M. ; et al J. Med. Chem. 2014, 57, 1812. doi: 10.1021/jm400201a
14	Siegel D. ; Hui H. C. ; Doerffler E. ; Clarke M. O. ; Chun K. ; Zhang L. ; Neville S. ; Carra E. ; Lew W. ; Ross B. ; et al J. Med. Chem. 2017, 60, 1648. doi: 10.1021/acs.jmedchem.6b01594
15	Kokic G. ; Hillen H. S. ; Tegunov D. ; Dienemann C. ; Seitz F. ; Schmitzova J. ; Farnung L. ; Siewert A. ; Höbartner C. ; Cramer P. Nat. Commun. 2021, 12, 279. doi: 10.1038/s41467-020-20542-0
16	Yuan S. ; Luo Y.-Q. ; Zuo J.-H. ; Liu H. ; Li F. ; Yu B. Eur. J. Med. Chem. 2021, 215, 113284. doi: 10.1016/j.ejmech.2021.113284
17	Wang M. ; Cao R. ; Zhang L. ; Yang X. ; Liu J. ; Xu M. ; Shi Z. ; Hu Z. ; Zhong W. ; Xiao G. Cell Res. 2020, 30, 269. doi: 10.1038/s41422-020-0282-0
18	Cadegiani F. A. ; do Nascimento Fonseca D. ; McCoy J. ; Zimerman R. A. ; Mirza F. N. ; do Nascimento Correia M. ; Barros R. N. ; Onety D. C. ; Israel K. C. P. ; de Almeida B. G. ; et al medRxiv. 2021, doi: 10.1101/2021.06.22.21259318
19	中华医学会感染病学分会艾滋病学组; 中国疾病预防控制中心. 协和医学杂志, 2019, 10 (1), 31.
20	Chang J.Acc. Chem. Res. 2022, 55, 565. doi: 10.1021/acs.accounts.1c00697
21	Yu B. ; Chang J.Sig. Transduct. Target Ther. 2020, 5, 236. doi: 10.1038/s41392-020-00351-z
22	Wang R.-R. ; Yang Q.-H. ; Luo R.-H. ; Peng Y.-M. ; Dai S.-X. ; Zhang X.-J. ; Chen H. ; Cui X.-Q. ; Liu Y.-J. ; Huang J.-F.; ; et al PLoS ONE 2014, 9, e105617. doi: 10.1371/journal.pone.0105617
23	Wang Q. ; Hu W. ; Wang S. ; Pan Z. ; Tao L. ; Guo X. ; Qian K. ; Chen C.-H. ; Lee K.-H. ; Chang J.Eur. J. Med. Chem. 2011, 46, 4178. doi: 10.1016/j.ejmech.2011.06.020
24	Hughes D. L. Org. Pro. Res. Dev. 2019, 23, 716. doi: 10.1021/acs.oprd.9b00031
25	Rawal R. K. ; Murugesan V. ; Katti S. B. Curr. Med. Chem. 2012, 19, 5364. doi: 10.2174/092986712803833326
26	Mordant C. ; Schmitt B. ; Pasquier E. ; Demestre C. ; Queguiner L. ; Masungi C. ; Peeters A. ; Smeulders L. ; Bettens E. ; Hertogs K. ; et al Eur. J. Med. Chem. 2007, 42, 567. doi: 10.1016/j.ejmech.2006.11.014
27	Wang T. ; Kadow J. F. ; Meanwell N. A. Med. Chem. Res. 2021, 30, 1955.
28	Langley D. R. ; Kimura S. R. ; Sivaprakasam P. ; Zhou N. ; Dicker I. ; McAuliffe B. ; Wang T. ; Kadow J. F. ; Meanwell N. A. ; Krystal M. Proteins 2015, 83, 331. doi: 10.1002/prot.24726
29	戴宇豪; 罗恺弘; 李国靖; 贾萌; 李建其; 刘育. 中国药物化学杂志, 2022, 32 (4), 293.
30	Johns B. A. ; Kawasuji T. ; Weatherhead J. G. ; Taishi T. ; Temelkoff D. P. ; Yoshida H. ; Akiyama T. ; Taoda Y. ; Murai H. ; Kiyama R. ; et al J. Med. Chem. 2013, 56, 5901. doi: 10.1021/jm400645w
31	Omoto S. ; Speranzini V. ; Hashimoto T. ; Noshi T. ; Yamaguchi H. ; Kawai M. ; Kawaguchi K. ; Uehara T. ; Shishido T. ; Naito A. ; et al Sci. Rep. 2018, 8, 9633. doi: 10.1038/s41598-018-27890-4
32	Makoto, K. Substituted Polycyclic Pyridone Derivatives and Prodrugs thereof. US10633397B2, 2020-04-28.
33	修思雨; 张健; 鞠翰; 贾瑞芳; 黄兵; 展鹏; 刘新泳. 药学学报, 2020, 55 (4), 611.
34	Noshi T. ; Kitano M. ; Taniguchi K. ; Yamamoto A. ; Omoto S. ; Baba K. ; Hashimoto T. ; Ishida K. ; Kushima Y. ; Hattori K. ; et al Antiviral Res. 2018, 160, 109. doi: 10.1016/j.antiviral.2018.10.008
35	曹瑞源; 赵磊; 钟武. 临床药物治疗杂志, 2018, 16 (1), 1.

药物	EC₅₀/(μmol∙L⁻¹)	CC₅₀/(μmol∙L⁻¹)	选择性因数SI
瑞德西韦	0.77	> 100	> 129.87
磷酸氯喹	1.13	> 100	> 88.50
法匹拉韦	61.88	> 400	> 6.46

HIV strain	31		34		35
HIV strain	EC₅₀/(nmol∙L⁻¹)	FC ^b	EC₅₀/(nmol∙L⁻¹)	FC	EC₅₀/(nmol∙L⁻¹)	FC
Wild type HIV-1_IIIB	0.11 ± 0.02	1	201.89 ± 34.11	1	9.39 ± 1.22	1
FNC_P-21 HIV-1_IIIB	80.82 ± 8.14	735	123,690 ± 18,321	613	12.29 ± 0.24	1.31
3TC_P-21 HIV-1_IIIB	25.49 ± 1.86	232	690,210 ± 64,066	3419	13.13 ± 2.43	1.40
HIV_LAI-M184V	27.45 ± 2.85	250	> 800,000	> 3963	8.21 ± 1.30	0.87

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