药学学报, 2020, 55(4): 611-626
引用本文:
修思雨, 张健, 鞠翰, 贾瑞芳, 黄兵, 展鹏, 刘新泳. 抗流感病毒药物靶标及其小分子抑制剂的研究进展[J]. 药学学报, 2020, 55(4): 611-626.
XIU Si-yu, ZHANG Jian, JU Han, JIA Rui-fang, HUANG Bing, ZHAN Peng, LIU Xin-yong. Progress on IFV drug targets and small molecule inhibitors[J]. Acta Pharmaceutica Sinica, 2020, 55(4): 611-626.

抗流感病毒药物靶标及其小分子抑制剂的研究进展
修思雨1, 张健1, 鞠翰1, 贾瑞芳1, 黄兵2, 展鹏1, 刘新泳1
1. 山东大学药学院药物化学研究所, 化学生物学教育部重点实验室, 山东 济南 250012;
2. 山东省农业科学院家禽研究所, 山东 济南 250012
摘要:
流感病毒(influenza virus,IFV)的暴发给人类的健康和生命造成了严重危害,致病性禽流感病毒(avian influenza virus,AIV)感染不断给人类带来致命性威胁,给世界各国带来极大的恐慌。随着流感病毒生物学特征的深入研究以及药物发现筛选技术的迅猛发展,新一代抗流感药物靶点及其抑制剂被陆续发现,为流感病毒的治疗方案提供了更多的选择。本综述精选近几年最具代表性的研究实例,从药物化学的视角总结了抗流感药物新靶标及其小分子抑制剂的研究进展。
关键词:    流感病毒      抗病毒药物      药物靶标      药物设计      小分子抑制剂     
Progress on IFV drug targets and small molecule inhibitors
XIU Si-yu1, ZHANG Jian1, JU Han1, JIA Rui-fang1, HUANG Bing2, ZHAN Peng1, LIU Xin-yong1
1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology(Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China;
2. Institute of Poultry Science, Shandong Academy of Agricultural Sciences, Jinan 250012, China
Abstract:
The outbreak of the influenza viruses (IFV) caused significant harm to our health and life. Human infections caused by pathogenic avian influenza virus (AIV) have continually brought great panic and death threats to people all over the world. With the in-depth study of the biological characteristics of influenza viruses and the rapid development of drug discovery screening technology, a new generation of anti-influenza drug targets and their inhibitors have been continuously discovered, providing more options for the treatment of influenza. From the point of view of medicinal chemistry, this review summarizes and discusses current endeavours towards the discovery and development of novel inhibitors and also provides examples illustrating new methodologies that contribute to the identification of novel anti-influenza drugs.
Key words:    influenza virus    antiviral drug    drug target    drug design    small molecule inhibitor   
收稿日期: 2019-09-09
DOI: 10.16438/j.0513-4870.2019-0737
基金项目: 国家自然科学基金面上项目(81773574);山东省重大科技创新工程(2019JZZY021011,2017CXGC1401);山东省农业科学院农业科技创新工程(CXGC2016B14);山东省农业重大应用技术创新项目(SD2019XM006).
通讯作者: 展鹏,Tel:86-531-88380270,E-mail:zhanpeng1982@sdu.edu.cn;刘新泳,E-mail:xinyongl@sdu.edu.cn
Email: zhanpeng1982@sdu.edu.cn;xinyongl@sdu.edu.cn
相关功能
PDF(1148KB) Free
打印本文
0
作者相关文章
修思雨  在本刊中的所有文章
张健  在本刊中的所有文章
鞠翰  在本刊中的所有文章
贾瑞芳  在本刊中的所有文章
黄兵  在本刊中的所有文章
展鹏  在本刊中的所有文章
刘新泳  在本刊中的所有文章

参考文献:
[1] Shen Z, Lou K, Wang W. New small-molecule drug design strategies for fighting resistant influenza A[J]. Acta Pharm Sin B, 2015, 5:419-430.
[2] Shin WJ, Seong BL. Novel antiviral drug discovery strategies to tackle drug-resistant mutants of influenza virus strains[J]. Expert Opin Drug Discov, 2019, 14:153-168.
[3] Peiris JS, Poon LL, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans[J]. J Clin Virol, 2009, 45:169-173.
[4] Moorthy NS, Poongavanam V, Pratheepa V. Viral M2 ion channel protein:a promising target for anti-influenza drug discovery[J]. Mini Rev Med Chem, 2014, 14:819-830.
[5] World Health Organization. Influenza (Seasonal)[DB/OL]. 2018[2018-11-6]. https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal).
[6] Bouvier NM, Palese P. The biology of influenza viruses[J]. Vaccine, 2008, 26:D49-D53.
[7] Taylor DN, Treanor JJ, Sheldon EA, et al. Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects[J]. Vaccine, 2007, 25:7656-7663.
[8] Lambert LC, Fauci AS. Influenza vaccines for the future[J]. N Engl J Med, 2010, 363:2036-2044.
[9] Goldhill DH, Te Velthuis AJW, Fletcher RA, et al. The mechanism of resistance to favipiravir in influenza[J]. Proc Natl Acad Sci U S A, 2018, 115:11613-11618.
[10] Leneva IA, Burtseva EI, Yatsyshina SB, et al. Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010-2011 influenza season in Russia[J]. Int J Infect Dis, 2016, 43:77-84.
[11] Haffizulla J, Hartman A, Hoppers M, et al. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza:a double-blind, randomised, placebo-controlled, phase 2b/3 trial[J]. Lancet Infect Dis, 2014, 14:609-618.
[12] Zhang C, Cao YL, Zhong W, et al. Establishment of a cell-based 2009 H1N1 influenza neuraminidase inhibitors evaluation system[J]. Acta Pharm Sin (药学学报), 2010, 45:383-387.
[13] Varghese JN, Laver WG, Colman PM, et al. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution[J]. Nature, 1983, 303:35-40.
[14] McAuley JL, Gilbertson BP, Trifkovic S, et al. Influenza virus neuraminidase structure and functions[J]. Front Microbiol, 2019, 10:39.
[15] Colman PM, Varghese JN, Laver WG, et al. Structure of the catalytic and antigenic sites in influenza virus neuraminidase[J]. Nature, 1983, 303:41-44.
[16] Palese P, Schulman JL, Bodo G, et al. Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA)[J]. Virology, 1974, 59:490-498.
[17] Nöhle U, Beau JM, Schauer R. Uptake, metabolism and excretion of orally and intravenously administered, double-labeled N-glycoloylneuraminic acid and single-labeled 2-deoxy-2,3-dehydro-N-acetylneuraminic acid in mouse and rat[J]. Eur J Biochem, 1982, 126:543-548.
[18] Von IM, Wu WY, Kok GB, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication[J]. Nature, 1993, 363:418-423.
[19] Cheer SM, Wagstaff AJ. Zanamivir:an update of its use in influenza[J]. Drugs, 2002, 62:71-106.
[20] Mcclellan K, Nz DC, Perry C. Oseltamivir:a review of its use in influenza[J]. Drugs, 2001, 61:263-283.
[21] Jefferson T, Demicheli V, Rivetti D, et al. Antivirals for influenza in healthy adults:systematic review[J]. Lancet, 2006, 367:303-313.
[22] Nuttapat A, Watshara S, Tanawut T, et al. Exploring the chemical space of influenza neuraminidase inhibitors[J]. PeerJ, 2016, 4:e1958.
[23] Chairat K, Tarning J, White NJ, et al. Pharmacokinetic properties of anti-influenza neuraminidase inhibitors[J]. J Clin Pharmacol, 2013, 53:119-139.
[24] Samson M, Pizzorno A, Abed Y, et al. Influenza virus resistance to neuraminidase inhibitors[J]. Antiviral Res, 2013, 98:174-185.
[25] Memoli MJ, Hrabal RJ, Hassantoufighi A, et al. Rapid selection of oseltamivir- and peramivir-resistant pandemic H1N1 virus during therapy in 2 immunocompromised hosts[J]. Clin Infect Dis, 2010, 50:1252-1255.
[26] Dapat C, Kondo H, Dapat IC, et al. Neuraminidase inhibitor susceptibility profile of pandemic and seasonal influenza viruses during the 2009-2010 and 2010-2011 influenza seasons in Japan[J]. Antiviral Res, 2013, 99:261-269.
[27] Collins PJ, Haire LF, Lin YP, et al. Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants[J]. Nature, 2008, 453:1258-1261.
[28] Shie JJ, Fang JM, Lai PT, et al. A practical synthesis of zanamivir phosphonate congeners with potent anti-influenza activity[J]. J Am Chem Soc, 2011, 133:17959-17965.
[29] Wang PC, Fang JM, Tsai KC, et al. Peramivir phosphonate derivatives as influenza neuraminidase inhibitors[J]. J Med Chem, 2016, 59:5297-5310.
[30] Xie Y, Xu D, Huang B, et al. Discovery of N-substituted oseltamivir derivatives as potent and selective inhibitors of H5N1 influenza neuraminidase[J]. J Med Chem, 2014, 57:8445-8458.
[31] Zhang J, Poongavanam V, Kang D, et al. Optimization of N-substituted oseltamivir derivatives as potent inhibitors of group-1 and -2 influenza A neuraminidases, including a drug-resistant variant[J]. J Med Chem, 2018, 61:6379-6397.
[32] Zhang J, Murugan NA, Tian Y, et al. Structure-based optimization of N-substituted oseltamivir derivatives as potent anti-influenza A virus agents with significantly improved potency against oseltamivir-resistant N1-H274Y variant[J]. J Med Chem, 2018, 61:9976-9999.
[33] Ju H, Zhang J, Sun Z, et al. Discovery of C-1 modified oseltamivir derivatives as potent influenza neuraminidase inhibitors[J]. Eur J Med Chem, 2018, 146:220-231.
[34] Jia R, Zhang J, Ai W, et al. Design, synthesis and biological evaluation of "Multi-Site"-binding influenza virus neuraminidase inhibitors[J]. Eur J Med Chem, 2019, 178:64-80.
[35] Acharya R, Carnevale V, Fiorin G, et al. Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus[J]. Proc Natl Acad Sci U S A, 2010, 107:15075-15080.
[36] Zhou Z, Liu T, Zhang J, et al. Influenza A virus polymerase:an attractive target for next-generation anti-influenza therapeutics[J]. Drug Discov Today, 2018, 23:503-518.
[37] Kumar B, Asha K, Khanna M, et al. The emerging influenza virus threat:status and new prospects for its therapy and control[J]. Arch Virol, 2018, 163:831-844.
[38] Bright RA, Medina MJ, Xu X, et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005:a cause for concern[J]. Lancet, 2005, 366:1175-1181.
[39] Bright RA, Shay DK, Shu B, et al. Adamantane resistance among influenza A viruses isolated early during the 2005-2006 influenza season in the United States[J]. JAMA, 2006, 295:891-894.
[40] Krumbholz A, Schmidtke M, Bergmann S, et al. High prevalence of amantadine resistance among circulating European porcine influenza A viruses[J]. J Gen Virol, 2009, 90:900-908.
[41] Wang J, Wu Y, Ma C, et al. Structure and inhibition of the drug-resistant S31N mutant of the M2 ion channel of influenza A virus[J]. Proc Natl Acad Sci U S A, 2013, 110:1315-1320.
[42] Naesens L, Stevaert A, Vanderlinden E. Antiviral therapies on the horizon for influenza[J]. Curr Opin Pharmacol, 2016, 30:106-115.
[43] Thomaston JL, Polizzi NF, Konstantinidi A, et al. Inhibitors of the M2 proton channel engage and disrupt transmembrane networks of hydrogen-bonded waters[J]. J Am Chem Soc, 2018, 140:15219-15226.
[44] Barniol-Xicota M, Gazzarrini S, Torres E, et al. Slow but steady wins the race:dissimilarities among new dual inhibitors of the wild-type and the V27A mutant M2 channels of influenza A virus[J]. J Med Chem, 2017, 60:3727-3738.
[45] Li F, Hu Y, Wang Y, et al. Expeditious lead optimization of isoxazole-containing influenza A virus M2-S31N inhibitors using the Suzuki-Miyaura cross-coupling reaction[J]. J Med Chem, 2017, 60:1580-1590.
[46] Wang J, Ma C, Fiorin G, et al. Molecular dynamics simulation directed rational design of inhibitors targeting drug-resistant mutants of influenza A virus M2[J]. J Am Chem Soc, 2011, 133:12834-12841.
[47] Rey-Carrizo M, Barniol-Xicota M, Ma C, et al. Easily accessible polycyclic amines that inhibit the wild-type and amantadine-resistant mutants of the M2 channel of influenza A virus[J]. J Med Chem, 2014, 57:5738-5747.
[48] Li F, Ma C, DeGrado WF, et al. Discovery of highly potent inhibitors targeting the predominant drug-resistant S31N mutant of the influenza A virus M2 proton channel[J]. J Med Chem, 2016, 59:1207-1216.
[49] Wang J, Ma C, Wang J, et al. Discovery of novel dual inhibitors of the wild-type and the most prevalent drug-resistant mutant, S31N, of the M2 proton channel from influenza A virus[J]. J Med Chem, 2013, 56:2804-2812.
[50] Wang Y, Hu Y, Xu S, et al. In vitro pharmacokinetic optimizations of AM2-S31N channel blockers led to the discovery of slow-binding inhibitors with potent antiviral activity against drug-resistant influenza A viruses[J]. J Med Chem, 2018, 61:1074-1085.
[51] Harrison SC. Viral membrane fusion[J]. Nat Struct Mol Biol, 2008, 15:690-698.
[52] Leneva IA, Falynskova IN, Makhmudova NR, et al. Umifenovir susceptibility monitoring and characterization of influenza viruses isolated during ARBITR clinical study[J]. J Med Virol, 2019, 91:588-597.
[53] Koszalka P, Tilmanis D, Hurt AC. Influenza antivirals currently in late-phase clinical trial[J]. Influenza Other Respir Viruses, 2017, 11:240-246.
[54] Kadam RU, Wilson IA. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol[J]. Proc Natl Acad Sci U S A, 2017, 114:206-214.
[55] Wright ZVF, Wu NC, Kadam RU, et al. Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin[J]. Bioorg Med Chem Lett, 2017, 27:3744-3748.
[56] Belardo G, Cenciarelli O, La Frazia S, et al. Synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza A viruses in vitro[J]. Antimicrob Agents Chemother, 2015, 59:1061-1069.
[57] Basu A, Antanasijevic A, Wang M, et al. New small molecule entry inhibitors targeting hemagglutinin-mediated influenza a virus fusion[J]. J Virol, 2014, 88:1447-1460.
[58] Basu A, Komazin-Meredith G, McCarthy C, et al. Molecular mechanism underlying the action of influenza A virus fusion inhibitor MBX2546[J]. ACS Infect Dis, 2017, 3:330-335.
[59] Plotch SJ, O'Hara B, Morin J, et al. Inhibition of influenza A virus replication by compounds interfering with the fusogenic function of the viral hemagglutinin[J]. J Virol, 1999, 73:140-151.
[60] Liu S, Li R, Zhang R, et al. CL-385319 inhibits H5N1 avian influenza A virus infection by blocking viral entry[J]. Eur J Pharmacol, 2011, 660:460-467.
[61] Leiva R, Barniol-Xicota M, Codony S, et al. Aniline-based inhibitors of influenza H1N1 virus acting on hemagglutinin-mediated fusion[J]. J Med Chem, 2018, 61:98-118.
[62] van Dongen MJP, Kadam RU, Juraszek J, et al. A small-molecule fusion inhibitor of influenza virus is orally active in mice[J]. Science, 2019, 363:eaar6221.
[63] Fleishman SJ, Whitehead TA, Ekiert DC, et al. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin[J]. Science, 2011, 332:816-821.
[64] Whitehead TA, Chevalier A, Song Y, et al. Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing[J]. Nat Biotechnol, 2012, 30:543-548.
[65] Ekiert DC, Bhabha G,Elsliger MA, et al. Antibody recognition of a highly conserved influenza virus epitope[J]. Science, 2009, 324:246-251.
[66] Zhao X, Li R, Zhou Y, et al. Discovery of highly potent pinanamine-based inhibitors against amantadine- and oseltamivir-resistant influenza A viruses[J]. J Med Chem, 2018, 61:5187-5198.
[67] TeVelthuis AJ, Robb NC,Kapanidis AN, et al. The role of the priming loop in influenza A virus RNA synthesis[J]. Nat Microbiol, 2016, 1:16029.
[68] Reich S, Guilligay D, Pflug A, et al. Structural insight into cap-snatching and RNA synthesis by influenza polymerase[J]. Nature, 2014, 516:361-366.
[69] Tarbet EB, Maekawa M, Furuta Y, et al. Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009(H1N1) virus infections in mice[J]. Antiviral Res, 2012, 94:103-110.
[70] Byrn RA, Jones SM, Bennett HB, et al. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit[J]. Antimicrob Agents Chemother, 2015, 59:1569-1582.
[71] U.S.N.L.o. Medicine. A Phase 2b, Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study of 2 Dose Levels of VX 787 Administered as Monotherapy and One Dose Level of VX-787 Administered in Combination With Oseltamivir for the Treatment of Acute Uncomplicated Seasonal Influenza A in Adult Subjects[DB/OL]. 2017[2017-6-14]. https://www.clinicaltrials.gov/ct2/show/NCT02342249?cond=VX-787&draw=1.
[72] U.S.N.L.o. Medicine. A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188(Baloxavir Marboxil) Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Otherwise Healthy Patients With Influenza[DB/OL]. 2019[2019-08-22]. https://www.clinicaltrials.gov/ct2/show/NCT02954354?cond=baloxavir.
[73] Noshi T, Kitano M, Taniguchi K, et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit[J]. Antiviral Res, 2018, 160:109-117.
[74] Credille CV, Chen Y, Cohen SM. Fragment-based identification of influenza endonuclease inhibitors[J]. J Med Chem, 2016, 59:6444-6454.
[75] Boivin S, Cusack S, Ruigrok RW, et al. Influenza A virus polymerase:structural insights into replication and host adaptation mechanisms[J]. J Biol Chem, 2010, 285:28411-28417.
[76] Massari S, Goracci L, Desantis J, et al. Polymerase acidic protein-basic protein 1(PA-PB1) protein-protein interaction as a target for next-generation anti-influenza therapeutics[J]. J Med Chem, 2016, 59:7699-7718.
[77] Obayashi E, Yoshida H, Kawai F, et al. The structural basis for an essential subunit interaction in influenza virus RNA polymerase[J]. Nature, 2008, 454:1127-1131.
[78] Muratore G, Goracci L, Mercorelli B, et al. Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase[J]. Proc Natl Acad Sci U S A, 2012, 109:6247-6252.
[79] Massari S, Nannetti G, Desantis J, et al. A broad anti-influenza hybrid small molecule that potently disrupts the interaction of polymerase acidic protein-basic protein 1(PA-PB1) subunits[J]. J Med Chem, 2015, 58:3830-3842.
[80] Desantis J, Nannetti G, Massari S, et al. Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity[J]. Eur J Med Chem, 2017, 138:128-139.
[81] Desantis J, Nannetti G, Massari S, et al. Corrigendum to "Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity"[Eur. J. Med. Chem. 138(2017) 128-139] [J]. Eur J Med Chem, 2018, 156:302-303.
[82] Nannetti G, Massari S, Mercorelli B, et al. Potent and broad-spectrum cycloheptathiophene-3-carboxamide compounds that target the PA-PB1 interaction of influenza virus RNA polymerase and possess a high barrier to drug resistance[J]. Antiviral Res, 2019, 165:55-64.
[83] Tintori C, Laurenzana I, Fallacara AL, et al. High-throughput docking for the identification of new influenza A virus polymerase inhibitors targeting the PA-PB1 protein-protein interaction[J]. Bioorg Med Chem Lett, 2014, 24:280-282.
[84] Pagano M, Castagnolo D, Bernardini M, et al. The fight against the influenza A virus H1N1:synthesis, molecular modeling, and biological evaluation of benzofurazan derivatives as viral RNA polymerase inhibitors[J]. ChemMedChem, 2014, 9:129-150.
[85] Trist IM, Nannetti G, Tintori C, et al. 4,6-Diphenylpyridines as Promising novel anti-influenza agents targeting the PA-PB1 protein-protein interaction:structure-activity relationships exploration with the aid of molecular modeling[J]. J Med Chem, 2016, 59:2688-2703.
[86] Zhang J, Hu Y, Foley C, et al. Exploring ugi-azide four-component reaction products for broad-spectrum influenza antivirals with a high genetic barrier to drug resistance[J]. Sci Rep, 2018, 8:4653.
[87] Yuan S, Chu H, Ye J, et al. Identification of a novel small-molecule compound targeting the influenza A virus polymerase PB1-PB2 interface[J]. Antiviral Res, 2017, 137:58-66.
[88] Amorim MJ, Read EK, Dalton RM, et al. Nuclear export of influenza A virus mRNAs requires ongoing RNA polymerase II activity[J]. Traffic, 2007, 8:1-11.
[89] Cianci C, Gerritz SW, Deminie C, et al. Influenza nucleoprotein:promising target for antiviral chemotherapy[J]. Antivir Chem Chemother, 2012, 23:77-91.
[90] Lejal N, Tarus B, Bouguyon E, et al. Structure-based discovery of the novel antiviral properties of naproxen against the nucleoprotein of influenza A virus[J]. Antimicrob Agents Chemother, 2013, 57:2231-2242.
[91] Zheng W, Fan W, Zhang S, et al. Naproxen exhibits broad anti-influenza virus activity in mice by impeding viral nucleoprotein nuclear export[J]. Cell Rep, 2019, 27:1875-1885.
[92] Dilly S,FotsoFotsoA, Lejal N, et al. From naproxen repurposing to naproxen analogues and their antiviral activity against influenza A virus[J]. J Med Chem, 2018, 61:7202-7217.
[93] Tarus B, Bertrand H, Zedda G, et al. Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus[J]. J Biomol Struct Dyn, 2015, 33:1899-1912.
[94] Gerritz SW, Cianci C, Kim S, et al. Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers[J]. Proc Natl Acad Sci U S A, 2011, 108:15366-15371.
[95] Cheng H, Wan J, Lin MI, et al. Design, synthesis, and in vitro biological evaluation of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents targeting virus nucleoprotein[J]. J Med Chem, 2012, 55:2144-2153.
[96] Liao JX, Cheng HM, Wan JT, et al. Evaluation of benzamide derivatives as new influenza A nucleoprotein inhibitors[J]. Open J Med Chem, 2016, 6:43-50.
[97] Perwitasari O, Johnson S, Yan X, et al. Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo[J]. J Virol, 2014, 88:10228-10243.
[98] Kakisaka M, Sasaki Y, Yamada K, et al. A novel antiviral target structure involved in the RNA binding, dimerization, and nuclear export functions of the influenza A virus nucleoprotein[J]. PLoS Pathog, 2015, 11:e1005062.
[99] Huang F, Chen J, Zhang J, et al. Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein[J]. J Cell Mol Med, 2018, 22:1826-1839.
[100] Sethy B, Hsieh CF, Lin TJ, et al. Design, synthesis, and biological evaluation of itaconic acid derivatives as potential anti-influenza agents[J]. J Med Chem, 2019, 62:2390-2403.
[101] White KM, Abreu P Jr, Wang H, et al. Broad spectrum inhibitor of influenza A and B viruses targeting the viral nucleoprotein[J]. ACS Infect Dis, 2018, 4:146-157.
相关文献:
1.魏粉菊, 马悦, 俞霁, 贾海永, 刘新泳, 展鹏.基于新靶标的HBV抑制剂研究进展(2):RNase H及其他靶标[J]. 药学学报, 2020,55(4): 566-574
2.魏文秀, 荆兰兰, 刘新泳, 展鹏.抗疱疹病毒药物化学研究新进展[J]. 药学学报, 2020,55(4): 575-584
3.李敬, 刘新泳, 展鹏.人巨细胞病毒抑制剂研究进展[J]. 药学学报, 2020,55(4): 585-596
4.李卓, 贾瑞芳, 展鹏, 刘新泳.寨卡病毒抑制剂研究新进展[J]. 药学学报, 2020,55(4): 627-639
5.宋淑, 高萍, 展鹏, 刘新泳.丙型肝炎病毒抑制剂研究进展[J]. 药学学报, 2020,55(4): 652-668
6.黄天广, 孙林, 展鹏, 刘新泳.广谱抗病毒药物研究进展[J]. 药学学报, 2020,55(4): 679-693
7.孙彦莹, 左晓芳, 展鹏, 刘新泳.抗腺病毒药物化学研究新进展[J]. 药学学报, 2020,55(4): 720-733
8.周忠霞, 孙林, 康东伟, 陈子慧, 唐苗苗, 李思雨, 展鹏, 刘新泳.具有新作用机制的HIV-1逆转录酶抑制剂研究进展[J]. 药学学报, 2018,53(5): 691-700
9.霍志鹏, 左晓芳, 康东伟, 展鹏, 刘新泳.抗艾滋病药物新靶标及其小分子抑制剂的研究进展[J]. 药学学报, 2018,53(3): 356-374