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{{NoteTA|G1=Medicine|G2=LS}}
{{Medical}}
{{Drugbox|drug_name=|type=|IUPAC_name=<nowiki>sodium (2S)-1-hydroxy-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-3-(2-oxopyrrolidin-3-yl)propane-1-sulfonate</nowiki>|image=GC376_structure.png
|alt=|caption=|tradename=|MedlinePlus=|licence_EU=|licence_US=|pregnancy_AU=|pregnancy_US=|pregnancy_category=|legal_US=Investigational drug|legal_status=|bioavailability=|metabolism=|elimination_half-life=|excretion=|CAS_number_Ref={{cascite|correct|CAS}}|CAS_number=1416992-39-6|UNII_Ref={{fdacite|correct|FDA}}|UNII=H1NMJ5XDG5|PubChem=71481119|ChEMBL=2315036|DrugBank=|ChemSpiderID=29396096

|C=21|H=30|N=3|Na=1|O=8|S=1|molecular_weight=|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+]|StdInChI=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|StdInChIKey=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|广谱]][[抗病毒药物]]，用于治疗人类和动物。<ref>{{Cite web |title=Anivive |url=https://www.anivive.com/coronavirus |access-date=2020-05-14 |website=www.anivive.com |archive-date=2021-11-24 |archive-url=https://web.archive.org/web/20211124171458/https://anivive.com/coronavirus |dead-url=no }}</ref>Anivive从[[堪萨斯州立大学]]获得了 GC376 的全球独家专利权。<ref>{{Cite web |last= |first= |date=September 20, 2018 |title=Anivive licenses antiviral drug for fatal cat disease |url=https://www.k-state.edu/media/newsreleases/2018-09/fipantiviral92018.html |url-status=no |archive-url=https://web.archive.org/web/20211124173616/https://www.k-state.edu/media/newsreleases/2018-09/fipantiviral92018.html |archive-date=2021-11-24 |access-date=2020-05-14 |website=www.k-state.edu }}</ref>截至2020年，GC376正在作为[[COVID-19]]的治疗药物进行研究。<ref name=":0" />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]]；<ref>{{cite journal |vauthors=Takahashi D, Kim Y, Lovell S, Prakash O, Groutas WC, Chang KO |date=December 2013 |title=Structural and inhibitor studies of norovirus 3C-like proteases |journal=Virus Research |volume=178 |issue=2 |pages=437–44 |doi=10.1016/j.virusres.2013.09.008 |pmc=3840063 |pmid=24055466}}</ref>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。<ref>{{cite journal |display-authors=6 |vauthors=Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, Bannasch M, Meadows JM, Chang KO |date=April 2018 |title=Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis |journal=Journal of Feline Medicine and Surgery |volume=20 |issue=4 |pages=378–392 |doi=10.1177/1098612X17729626 |pmc=5871025 |pmid=28901812}}</ref>其他研究支持用于[[猪流行性腹泻病毒]]。<ref name="PEDV">{{cite journal |vauthors=Ye G, Wang X, Tong X, Shi Y, Fu ZF, Peng G |date=February 2020 |title=Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376 |journal=Viruses |volume=12 |issue=2 |pages=240 |doi=10.3390/v12020240 |pmc=7077318 |pmid=32098094 |doi-access=free}}</ref>

== COVID-19 ==
[[File:Viruses-12-00240-g004.png|thumb|260x260px|与GC376复合的猪流行性腹泻病毒3C样蛋白酶的晶体结构。<ref name="PEDV" />]]
由于GC376显示出对冠状病毒的广谱活性，<ref name="pmid32006468">{{cite journal |vauthors=Pillaiyar T, Meenakshisundaram S, Manickam M |date=April 2020 |title=Recent discovery and development of inhibitors targeting coronaviruses |journal=Drug Discovery Today |volume=25 |issue=4 |pages=668–688 |doi=10.1016/j.drudis.2020.01.015 |pmc=7102522 |pmid=32006468}}</ref>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。<ref name="pmid32022370">{{cite journal |vauthors=Morse JS, Lalonde T, Xu S, Liu WR |date=March 2020 |title=Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV |journal=ChemBioChem |volume=21 |issue=5 |pages=730–738 |doi=10.1002/cbic.202000047 |pmc=7162020 |pmid=32022370 |doi-access=free}}</ref>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。<ref>{{cite journal |last1=Ma |first1=Chunlong |last2=Sacco |first2=Michael D. |last3=Hurst |first3=Brett |last4=Townsend |first4=Julia A. |last5=Hu |first5=Yanmei |last6=Szeto |first6=Tommy |last7=Zhang |first7=Xiujun |last8=Tarbet |first8=Bart |last9=Marty |first9=Michael T. |last10=Chen |first10=Yu |last11=Wang |first11=Jun |date=20 April 2020 |title=Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease |journal=bioRxiv |doi=10.1101/2020.04.20.051581 |pmc=7263507 |pmid=32511378 |s2cid=216145410 |doi-access=free}}</ref>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。<ref name="Vuong">{{cite journal |last1=Vuong |first1=Wayne |last2=Khan |first2=Muhammad Bashir |last3=Fischer |first3=Conrad |last4=Arutyunova |first4=Elena |last5=Lamer |first5=Tess |last6=Shields |first6=Justin |last7=Saffran |first7=Holly A. |last8=McKay |first8=Ryan T. |last9=van Belkum |first9=Marco J. |last10=Joyce |first10=Michael A. |last11=Young |first11=Howard S. |date=December 2020 |title=Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication |journal=Nature Communications |volume=11 |issue=1 |pages=4282 |doi=10.1038/s41467-020-18096-2 |pmc=7453019 |pmid=32855413 |s2cid=218551888 |doi-access=free |last12=Tyrrell |first12=D. Lorne |last13=Vederas |first13=John C. |last14=Lemieux |first14=M. Joanne}}</ref>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”。<ref name=":0">{{Citation|title=Brent Stockwell, COVID-19 Virtual Symposium May 6, 2020|url=https://www.youtube.com/watch?v=QfsEXwx22EM|language=en|access-date=2020-05-14|archive-date=2021-11-24|archive-url=https://web.archive.org/web/20211124173614/https://www.youtube.com/watch?v=QfsEXwx22EM|dead-url=no}}</ref>

== 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[[巴尔的摩病毒分类系统#第四组:正单链RNA病毒(+)ssRNA viruses|(+)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[[缩硫醛|单缩硫醛]]并阻断酶的正常功能。<ref name="PEDV" /><ref name="Vuong" />

== 参见 ==

* [[3CLpro-1]]
* [[卡莫氟]]
* [[依布硒]]
* [[GRL-0617]]
* [[芦平曲韦]]
* [[茶黄素双没食子酸酯]]
* [[奈玛特韦]]

== 参考文献 ==
{{Reflist}}

== 外部链接 ==

* [https://www.anivive.com/ Anivive Pharmaceuticals] {{Wayback|url=https://www.anivive.com/ |date=20211124171503 }}

[[Category:苄酯]]
[[Category:氨基甲酸酯]]
[[Category:磺酸盐]]
[[Category:有机酸钠盐]]
[[Category:抗病毒药物]]

GC376 - 版本历史

imported>微肿头龙 来自 2023年6月29日 (四) 12:25

imported>微肿头龙来自 2023年6月29日 (四) 12:25