GC376

GC376
法律規範狀態
法律規範	美：Investigational drug;
識別資訊
	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號	1416992-39-6
PubChem CID	71481119;
ChemSpider	29396096;
UNII	H1NMJ5XDG5;
ChEMBL	ChEMBL2315036;
化學資訊
化學式	C21H30N3NaO8S
摩爾質量	507.53 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	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是生物製藥公司Anivive Lifesciences正在開發的一種廣譜抗病毒藥物，用於治療人類和動物。^[1]Anivive從堪薩斯州立大學獲得了 GC376 的全球獨家專利權。^[2]截至2020年，GC376正在作為COVID-19的治療藥物進行研究。^[3]GC376顯示出對許多人類和動物病毒的活性，包括冠狀病毒和諾如病毒；^[4]最廣泛的研究是在貓身上進行多項體內研究，以治療可導致致命的貓傳染性腹膜炎的冠狀病毒。^[5]其他研究支持用於豬流行性腹瀉病毒。^[6]

COVID-19

由於GC376顯示出對冠狀病毒的廣譜活性，^[7]在2020年大流行初期，有人建議將其作為COVID-19的潛在治療方法。^[8]為應對危機，亞利桑那大學的研究人員發表了體外研究，表明GC376對SARS-CoV-2中的3C樣蛋白酶具有高度活性。^[9]由大衛·洛恩·泰瑞爾領導的另一組阿爾伯塔大學病毒學家隨後發表了一份單獨的出版物，證實了GC376對SARS-CoV-2中的3CLpro的活性，並表明GC376具有強大的抗病毒作用。^[10]第二天，哥倫比亞大學的祖克曼研究所舉辦了一場COVID-19虛擬研討會，該研討會發佈了由何大一領導的研究，並將GC376描述為何大一的實驗室正在研究的「最有前途」的蛋白酶抑制劑，因為GC376是「最有效的」並且在感染SARS-CoV-2的細胞培養物中達到了「完全病毒抑制」。^[3]

藥理

藥效學

GC376是一種蛋白酶抑制劑。它阻斷3C樣蛋白酶，一種常見於許多(+)ssRNA病毒的蛋白酶，從而阻止病毒多蛋白成熟為其功能部分。在化學上，GC376是醛GC373的亞硫酸氫根加合物，而它則作為該化合物的前藥。這種醛與蛋白酶活性位點的半胱氨酸144殘基形成共價鍵，產生單縮硫醛並阻斷酶的正常功能。^[6]^[10]

參見

參考文獻

^ Anivive. www.anivive.com. [2020-05-14]. （原始內容存檔於2021-11-24）.
^ Anivive licenses antiviral drug for fatal cat disease. www.k-state.edu. September 20, 2018 [2020-05-14]. （原始內容存檔於2021-11-24）.
^ ^3.0 ^3.1 Brent Stockwell, COVID-19 Virtual Symposium May 6, 2020, [2020-05-14], （原始內容存檔於2021-11-24）（英語）
^ 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 .

外部連結

Anivive Pharmaceuticals （頁面存檔備份，存於互聯網檔案館）

[1] Anivive. www.anivive.com. [2020-05-14]. （原始內容存檔於2021-11-24）.

[2] Anivive licenses antiviral drug for fatal cat disease. www.k-state.edu. September 20, 2018 [2020-05-14]. （原始內容存檔於2021-11-24）.

[:0-3] 3.0 ^3.1 Brent Stockwell, COVID-19 Virtual Symposium May 6, 2020, [2020-05-14], （原始內容存檔於2021-11-24）（英語）

[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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