GC376

GC376
法律规范状态
法律规范	美：Investigational drug;
识别信息
	IUPAC命名法 sodium (2S)-1-hydroxy-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonate; ;
CAS号	1416992-39-6
PubChem CID	71481119;
ChemSpider	29396096;
UNII	H1NMJ5XDG5;
ChEMBL	ChEMBL2315036;
化学信息
化学式	C21H30N3NaO8S
摩尔质量	507.53 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES CC(C)C[C@@H](C(=O)N[C@@H](CC1CCNC1=O)C(O)S(=O)(=O)[O-])NC(=O)OCC2=CC=CC=C2.[Na+];
	InChI InChI=1S/C21H31N3O8S.Na/c1-13(2)10-16(24-21(28)32-12-14-6-4-3-5-7-14)19(26)23-17(20(27)33(29,30)31)11-15-8-9-22-18(15)25;/h3-7,13,15-17,20,27H,8-12H2,1-2H3,(H,22,25)(H,23,26)(H,24,28)(H,29,30,31);/q;+1/p-1/t15?,16-,17-,20?;/m0./s1; Key:BSPJDKCMFIPBAW-JPBGFCRCSA-M;

GC376是生物制药公司Anivive Lifesciences正在开发的一种广谱抗病毒药物，用于治疗人类和动物。^[1]Anivive从堪萨斯州立大学获得了 GC376 的全球独家专利权。^[2]截至2020年，GC376正在作为COVID-19的治疗药物进行研究。^[3]GC376显示出对许多人类和动物病毒的活性，包括冠状病毒和诺如病毒；^[4]最广泛的研究是在猫身上进行多项体内研究，以治疗可导致致命的猫传染性腹膜炎的冠状病毒。^[5]其他研究支持用于猪流行性腹泻病毒。^[6]

COVID-19

由于GC376显示出对冠状病毒的广谱活性，^[7]在2020年大流行初期，有人建议将其作为COVID-19的潜在治疗方法。^[8]为应对危机，亚利桑那大学的研究人员发表了体外研究，表明GC376对SARS-CoV-2中的3C样蛋白酶具有高度活性。^[9]由大卫·洛恩·泰瑞尔领导的另一组阿尔伯塔大学病毒学家随后发表了一份单独的出版物，证实了GC376对SARS-CoV-2中的3CLpro的活性，并表明GC376具有强大的抗病毒作用。^[10]第二天，哥伦比亚大学的祖克曼研究所举办了一场COVID-19虚拟研讨会，该研讨会发布了由何大一领导的研究，并将GC376描述为何大一的实验室正在研究的“最有前途”的蛋白酶抑制剂，因为GC376是“最有效的”并且在感染SARS-CoV-2的细胞培养物中达到了“完全病毒抑制”。^[3]

药理

药效学

GC376是一种蛋白酶抑制剂。它阻断3C样蛋白酶，一种常见于许多(+)ssRNA病毒的蛋白酶，从而阻止病毒多蛋白成熟为其功能部分。在化学上，GC376是醛GC373的亚硫酸氢根加合物，而它则作为该化合物的前药。这种醛与蛋白酶活性位点的半胱氨酸144残基形成共价键，产生单缩硫醛并阻断酶的正常功能。^[6]^[10]

参见

参考文献

^ Anivive. www.anivive.com. [2020-05-14]. （原始内容存档于2021-11-24）.
^ Anivive licenses antiviral drug for fatal cat disease. www.k-state.edu. September 20, 2018 [2020-05-14]. （原始内容存档于2021-11-24）.
^ ^3.0 ^3.1 Brent Stockwell, COVID-19 Virtual Symposium May 6, 2020, [2020-05-14], （原始内容存档于2021-11-24）（英语）
^ Takahashi D, Kim Y, Lovell S, Prakash O, Groutas WC, Chang KO. Structural and inhibitor studies of norovirus 3C-like proteases. Virus Research. December 2013, 178 (2): 437–44. PMC 3840063 . PMID 24055466. doi:10.1016/j.virusres.2013.09.008.
^ Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, et al. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. Journal of Feline Medicine and Surgery. April 2018, 20 (4): 378–392. PMC 5871025 . PMID 28901812. doi:10.1177/1098612X17729626.
^ ^6.0 ^6.1 ^6.2 Ye G, Wang X, Tong X, Shi Y, Fu ZF, Peng G. Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376. Viruses. February 2020, 12 (2): 240. PMC 7077318 . PMID 32098094. doi:10.3390/v12020240 .
^ Pillaiyar T, Meenakshisundaram S, Manickam M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discovery Today. April 2020, 25 (4): 668–688. PMC 7102522 . PMID 32006468. doi:10.1016/j.drudis.2020.01.015.
^ Morse JS, Lalonde T, Xu S, Liu WR. Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. ChemBioChem. March 2020, 21 (5): 730–738. PMC 7162020 . PMID 32022370. doi:10.1002/cbic.202000047 .
^ Ma, Chunlong; Sacco, Michael D.; Hurst, Brett; Townsend, Julia A.; Hu, Yanmei; Szeto, Tommy; Zhang, Xiujun; Tarbet, Bart; Marty, Michael T.; Chen, Yu; Wang, Jun. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. bioRxiv. 20 April 2020. PMC 7263507 . PMID 32511378. S2CID 216145410. doi:10.1101/2020.04.20.051581 .
^ ^10.0 ^10.1 Vuong, Wayne; Khan, Muhammad Bashir; Fischer, Conrad; Arutyunova, Elena; Lamer, Tess; Shields, Justin; Saffran, Holly A.; McKay, Ryan T.; van Belkum, Marco J.; Joyce, Michael A.; Young, Howard S.; Tyrrell, D. Lorne; Vederas, John C.; Lemieux, M. Joanne. Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nature Communications. December 2020, 11 (1): 4282. PMC 7453019 . PMID 32855413. S2CID 218551888. doi:10.1038/s41467-020-18096-2 .

外部链接

Anivive Pharmaceuticals （页面存档备份，存于互联网档案馆）

[1] Anivive. www.anivive.com. [2020-05-14]. （原始内容存档于2021-11-24）.

[2] Anivive licenses antiviral drug for fatal cat disease. www.k-state.edu. September 20, 2018 [2020-05-14]. （原始内容存档于2021-11-24）.

[:0-3] 3.0 ^3.1 Brent Stockwell, COVID-19 Virtual Symposium May 6, 2020, [2020-05-14], （原始内容存档于2021-11-24）（英语）

[4] Takahashi D, Kim Y, Lovell S, Prakash O, Groutas WC, Chang KO. Structural and inhibitor studies of norovirus 3C-like proteases. Virus Research. December 2013, 178 (2): 437–44. PMC 3840063 . PMID 24055466. doi:10.1016/j.virusres.2013.09.008.

[5] Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, et al. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. Journal of Feline Medicine and Surgery. April 2018, 20 (4): 378–392. PMC 5871025 . PMID 28901812. doi:10.1177/1098612X17729626.

[PEDV-6] 6.0 ^6.1 ^6.2 Ye G, Wang X, Tong X, Shi Y, Fu ZF, Peng G. Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376. Viruses. February 2020, 12 (2): 240. PMC 7077318 . PMID 32098094. doi:10.3390/v12020240 .

[pmid32006468-7] Pillaiyar T, Meenakshisundaram S, Manickam M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discovery Today. April 2020, 25 (4): 668–688. PMC 7102522 . PMID 32006468. doi:10.1016/j.drudis.2020.01.015.

[pmid32022370-8] Morse JS, Lalonde T, Xu S, Liu WR. Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. ChemBioChem. March 2020, 21 (5): 730–738. PMC 7162020 . PMID 32022370. doi:10.1002/cbic.202000047 .

[9] Ma, Chunlong; Sacco, Michael D.; Hurst, Brett; Townsend, Julia A.; Hu, Yanmei; Szeto, Tommy; Zhang, Xiujun; Tarbet, Bart; Marty, Michael T.; Chen, Yu; Wang, Jun. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. bioRxiv. 20 April 2020. PMC 7263507 . PMID 32511378. S2CID 216145410. doi:10.1101/2020.04.20.051581 .

[Vuong-10] 10.0 ^10.1 Vuong, Wayne; Khan, Muhammad Bashir; Fischer, Conrad; Arutyunova, Elena; Lamer, Tess; Shields, Justin; Saffran, Holly A.; McKay, Ryan T.; van Belkum, Marco J.; Joyce, Michael A.; Young, Howard S.; Tyrrell, D. Lorne; Vederas, John C.; Lemieux, M. Joanne. Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nature Communications. December 2020, 11 (1): 4282. PMC 7453019 . PMID 32855413. S2CID 218551888. doi:10.1038/s41467-020-18096-2 .

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