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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022

Author(s): Roberto Romeo, Laura Legnani, Maria Assunta Chiacchio, Salvatore V. Giofrè and Daniela Iannazzo*

Volume 31, Issue 18, 2024

Published on: 12 September, 2023

Page: [2507 - 2549] Pages: 43

DOI: 10.2174/0929867331666230907093501

Price: $65

Abstract

In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNAdependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.

« Previous Next »
[1]
Hu, B.; Guo, H.; Zhou, P.; Shi, Z.L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol., 2021, 19(3), 141-154.
[http://dx.doi.org/10.1038/s41579-020-00459-7] [PMID: 33024307]
[2]
Krammer, F.; Smith, G.J.D.; Fouchier, R.A.M.; Peiris, M.; Kedzierska, K.; Doherty, P.C.; Palese, P.; Shaw, M.L.; Treanor, J.; Webster, R.G.; García-Sastre, A. Influenza. Nat. Rev. Dis. Primer, 2018, 4, 3.
[http://dx.doi.org/10.1038/s41572-018-0002-y]
[3]
Dini, G.; Toletone, A.; Sticchi, L.; Orsi, A.; Bragazzi, N.L.; Durando, P. Influenza vaccination in healthcare workers: A comprehensive critical appraisal of the literature. Hum. Vaccin. Immunother., 2018, 14(3), 772-789.
[http://dx.doi.org/10.1080/21645515.2017.1348442]
[4]
Świerczyńska, M.; Mirowska-Guzel, D.M.; Pindelska, E. Antiviral drugs in influenza. Int. J. Environ. Res. Public Health, 2022, 19(5), 3018.
[http://dx.doi.org/10.3390/ijerph19053018] [PMID: 35270708]
[5]
Bouvier, N.M.; Palese, P. The biology of influenza viruses. Vaccine, 2008, 26(Suppl 4)(4), D49-D53.
[http://dx.doi.org/10.1016/j.vaccine.2008.07.039] [PMID: 19230160]
[6]
Pritchett, T.J.; Brossmer, R.; Rose, U.; Paulson, J.C. Recognition of monovalent sialosides by influenza virus H3 hemagglutinin. Virology, 2022, 160(2), 502-506.
[http://dx.doi.org/10.1016/0042-6822(87)90026-2]
[7]
Principi, N.; Camilloni, B.; Alunno, A.; Polinori, I.; Argentiero, A.; Esposito, S. Drugs for influenza treatment: Is there significant news? Front. Med., 2019, 6, 109.
[http://dx.doi.org/10.3389/fmed.2019.00109] [PMID: 31192211]
[8]
Lampejo, T. Influenza and antiviral resistance: An overview. Eur. J. Clin. Microbiol. Infect. Dis., 2020, 39(7), 1201-1208.
[http://dx.doi.org/10.1007/s10096-020-03840-9] [PMID: 32056049]
[9]
Mahal, A.; Duan, M.; Zinad, D.S.; Mohapatra, R.K.; Obaidullah, A.J.; Wei, X.; Pradhan, M.K.; Das, D.; Kandi, V.; Zinad, H.S.; Zhu, Q. Recent progress in chemical approaches for the development of novel neuraminidase inhibitors. RSC Advances, 2021, 11(3), 1804-1840.
[http://dx.doi.org/10.1039/D0RA07283D] [PMID: 35424082]
[10]
Liu, S.; Wang, W.; Jiang, L.; Wan, S.; Zhang, L.; Yu, R.; Jiang, T. 2-Pyridinyl-4(3H)-quinazolinone: A scaffold for anti-influenza A virus compounds. Chem. Biol. Drug Des., 2015, 86(5), 1221-1225.
[http://dx.doi.org/10.1111/cbdd.12589] [PMID: 26017319]
[11]
Wang, P-C.; Fang, J-M.; Tsai, K-C.; Wang, S-Y.; Huang, W-I.; Tseng, Y.C.; Cheng, Y.S.; Cheng, E.; Cheng, T.J.; Cheng, R.; Wong, C.H. Peramivir phosphonate derivatives as influenza neuraminidase inhibitors. J. Med. Chem., 2016, 59, 5297-5310.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00029] [PMID: 27167096]
[12]
Abd El-All, A.S.; Atta, S.M.; Hanaa, M.F. R.; Enas M, A.; Abdalla, M.M. New potent SARS-CoV 3C-like protease inhibitors derived from thieno[2,3-d]-pyrimidine derivatives. Arch. Pharm. Chem., 2016, 349, 202-210.
[http://dx.doi.org/10.1002/ardp.201500407] [PMID: 26806115]
[13]
Enkhtaivan, G.; Muthuraman, P.; Kim, D.H.; Mistry, B. Discovery of berberine based derivatives as anti-influenza agent through blocking of neuraminidase. Bioorg. Med. Chem., 2017, 25(20), 5185-5193.
[http://dx.doi.org/10.1016/j.bmc.2017.07.006] [PMID: 28958846]
[14]
Mistry, B.; Patel, R.V.; Keum, Y.S.; Kim, D.H. Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects. Saudi J. Biol. Sci., 2017, 24(1), 36-44.
[http://dx.doi.org/10.1016/j.sjbs.2015.09.005] [PMID: 28053569]
[15]
Ju, H.; Zhang, J.; Sun, Z.; Huang, Z.; Qi, W.; Huang, B.; Zhan, P.; Liu, X. Discovery of C-1 modified oseltamivir derivatives as potent influenza neuraminidase inhibitors. Eur. J. Med. Chem., 2018, 146, 220-231.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.050] [PMID: 29407952]
[16]
Das, A.; Adak, A.K.; Ponnapalli, K.; Lin, C.H.; Hsu, K.C.; Yang, J.M.; Hsu, T.A.; Lin, C.C. Design and synthesis of 1,2,3-triazole-containing N-acyl zanamivir analogs as potent neuraminidase inhibitors. Eur. J. Med. Chem., 2016, 123, 397-406.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.064] [PMID: 27487569]
[17]
Chen, B.L.; Wang, Y.J.; Guo, H.; Zeng, G.Y. Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors. Eur. J. Med. Chem., 2016, 109, 199-205.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.031] [PMID: 26774928]
[18]
Meng, F.J.; Sun, T.; Dong, W.Z.; Li, M.H.; Tuo, Z.Z. Discovery of novel pyrazole derivatives as potent neuraminidase inhibitors against influenza H1N1 virus. Arch. Pharm., 2016, 349(3), 168-174.
[http://dx.doi.org/10.1002/ardp.201500342] [PMID: 26797880]
[19]
Shih, S.R.; Chu, T.Y.; Reddy, G.R.; Tseng, S.N.; Chen, H.L.; Tang, W.F.; Wu, M.; Yeh, J.Y.; Chao, Y.S.; Hsu, J.T.A.; Hsieh, H.P.; Horng, J.T. Pyrazole compound BPR1P0034 with potent and selective anti-influenza virus activity. J. Biomed. Sci., 2010, 17(1), 13.
[http://dx.doi.org/10.1186/1423-0127-17-13] [PMID: 20178582]
[20]
Sharma, G.; Vasanth Kumar, S.; Wahab, H.A. Molecular docking, synthesis, and biological evaluation of naphthoquinone as potential novel scaffold for H5N1 neuraminidase inhibition. J. Biomol. Struct. Dyn., 2018, 36(1), 233-242.
[http://dx.doi.org/10.1080/07391102.2016.1274271] [PMID: 28013578]
[21]
Yang, Z-L.; Zeng, X.; Liu, F. H, P.; Yu, Q.; Meng, X.; Yan, Z.-L.; Fan, Z.-C.; Xiao, H.-X.; Iyer, H.-X.; Yang, Y.; Yu, P. Synthesis of multivalent difluorinated zanamivir analogs as potent antiviral inhibitors. Tetrahedron Lett., 2016, 57, 2579-2582.
[http://dx.doi.org/10.1016/j.tetlet.2016.04.079]
[22]
Li, Z.; Meng, Y.; Xu, S.; Shen, W.; Meng, Z.; Wang, Z.; Ding, G.; Huang, W.; Xiao, W.; Xu, J. Discovery of acylguanidine oseltamivir carboxylate derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem., 2017, 25(10), 2772-2781.
[http://dx.doi.org/10.1016/j.bmc.2017.03.052] [PMID: 28385598]
[23]
Weiss, S.; Keller, M.; Bernhardt, G.; Buschauer, A.; König, B. NG-Acyl-argininamides as NPY Y1 receptor antagonists: Influence of structurally diverse acyl substituents on stability and affinity. Bioorg. Med. Chem., 2010, 18(17), 6292-6304.
[http://dx.doi.org/10.1016/j.bmc.2010.07.028] [PMID: 20688523]
[24]
Wang, Z.; Cheng, L.P.; Zhang, X.H.; Pang, W.; Li, L.; Zhao, J.L. Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(24), 5429-5435.
[http://dx.doi.org/10.1016/j.bmcl.2017.11.003] [PMID: 29141777]
[25]
Wang, K.; Yang, F.; Wang, L.; Liu, K.; Sun, L.; Lin, B.; Hu, Y.; Wang, B.; Cheng, M.; Tian, Y. Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors. Eur. J. Med. Chem., 2017, 141, 648-656.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.004] [PMID: 29107426]
[26]
Xiao, M.; Ye, J.; Lian, W.; Zhang, M.; Li, B.; Liu, A.; Hu, A. Microwave-assisted synthesis, characterization and bioassay of acylhydrazone derivatives as influenza neuraminidase inhibitors. Med. Chem. Res., 2017, 26(12), 3216-3227.
[http://dx.doi.org/10.1007/s00044-017-2015-6]
[27]
Zhang, J.; Poongavanam, V.; Kang, D.; Bertagnin, C.; Lu, H.; Kong, X.; Ju, H.; Lu, X.; Gao, P.; Tian, Y.; Jia, H.; Desta, S.; Ding, X.; Sun, L.; Fang, Z.; Huang, B.; Liang, X.; Jia, X.; Ma, X.; Xu, W.; Murugan, N.A.; Loregian, B.; Zhan, P.; Liu, X. Optimization of n-substituted oseltamivir derivatives as potent inhibitors of group-1 and -2 influenza A neuraminidases, including a drug-resistant variant. J. Med. Chem., 2018, 61, 6379-6397.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00929]
[28]
Neri-Bazán, R.M.; García-Machorro, J.; Méndez-Luna, D.; Tolentino-López, L.E.; Martínez-Ramos, F.; Padilla-Martínez, I.I.; Aguilar-Faisal, L.; Soriano-Ursúa, M.A.; Trujillo-Ferrara, J.G.; Fragoso-Vázquez, M.J.; Barrón, B.L.; Correa-Basurto, J. Design, in silico studies, synthesis and in vitro evaluation of oseltamivir derivatives as inhibitors of neuraminidase from influenza A virus H1N1. Eur. J. Med. Chem., 2017, 128, 154-167.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.039] [PMID: 28182988]
[29]
Hajzer, V.; Fišera, R.; Latika, A.; Durmis, J.; Kollár, J.; Frecer, V.; Tučeková, Z.; Miertuš, S.; Kostolanský, F.; Varečkovág, E.; Šebesta, R. Stereoisomers of oseltamivir: Synthesis, in silico prediction and biological evaluation. Org. Biomol. Chem., 2017, 15, 1828-1841.
[http://dx.doi.org/10.1039/c6ob02673g] [PMID: 28155963]
[30]
Vavricka, C.J.; Muto, C.; Hasunuma, T.¸.; Kimura, Y.; Araki, M.; Wu, Y.; Gao, G.F.; Ohrui, H.; Izumi, M.; Kiyota, H. Synthesis of sulfo-sialic acid analogues: Potent neuraminidase inhibitors in regards to anomeric functionality. Sci. Rep., 2017, 7, 8239.
[http://dx.doi.org/10.1038/s41598-017-07836-y] [PMID: 28811524]
[31]
Cheng, L.P.; Wang, T.C.; Yu, R.; Li, M.; Huang, J.W. Design, synthesis and biological evaluation of novel zanamivir derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem. Lett., 2018, 28(23-24), 3622-3629.
[http://dx.doi.org/10.1016/j.bmcl.2018.10.040] [PMID: 30389293]
[32]
Wang, B.; Wang, K.; Meng, P.; Hu, Y.; Yang, F.; Liu, K.; Lei, Z.; Chen, B.; Tian, Y. Design, synthesis, and evaluation of carboxyl-modified oseltamivir derivatives with improved lipophilicity as neuraminidase inhibitors. Bioorg. Med. Chem. Lett., 2018, 28(21), 3477-3482.
[http://dx.doi.org/10.1016/j.bmcl.2018.09.014] [PMID: 30266543]
[33]
Lin, D.; Yi, Y-J.; Xiao, M-W.; Chen, J.; Ye, J.; Hu, A-X.; Lian, W-W.; Liu, A-L.; Du, G-H. Design, synthesis and biological evaluation of honokiol derivatives as influenza neuraminidase inhibitors. J. Asian Nat. Prod. Res., 2019, 21, 1052-1067.
[http://dx.doi.org/10.1080/10286020.2018.1509854] [PMID: 30585512]
[34]
Tsuji, M.; Sriwilaijaroen, N.; Inoue, H.; Miki, K.; Kinoshita, K.; Koyama, K.; Furuhata, K.; Suzuki, Y.; Takahashi, K. Synthesis and anti-influenza virus evaluation of triterpene-sialic acid conjugates. Bioorg. Med. Chem., 2018, 26(1), 17-24.
[http://dx.doi.org/10.1016/j.bmc.2017.09.038] [PMID: 29198893]
[35]
Hadházi, Á.; Li, L.; Bailly, B.; Maggioni, A.; Martin, G.; Dirr, L.; Dyason, J.C.; Thomson, R.J.; Gao, G.F.; Borbás, A.; Ve, T.; Pascolutti, M.; von Itzstein, M. A sulfonozanamivir analogue has potent anti-influenza virus activity. ChemMedChem, 2018, 13(8), 785-789.
[http://dx.doi.org/10.1002/cmdc.201800092] [PMID: 29453852]
[36]
Jia, R.; Zhang, J.; Ai, W.; Ding, X.; Desta, S.; Sun, L.; Sun, Z.; Ma, X.; Li, Z.; Wang, D.; Huang, B.; Zhan, P.; Liu, X. Design, synthesis and biological evaluation of “Multi-Site”-binding influenza virus neuraminidase inhibitors. Eur. J. Med. Chem., 2019, 178, 64-80.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.076] [PMID: 31176096]
[37]
Cui, M.Y.; Xiao, M.W.; Xu, L.J.; Chen, Y.; Liu, A.L.; Ye, J.; Hu, A.X. Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors. Arch. Pharm., 2020, 353(1), 1900174.
[http://dx.doi.org/10.1002/ardp.201900174] [PMID: 31657061]
[38]
Ye, J.; Yang, X.; Xu, M.; Chan, P.; Ma, C. Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies. Eur. J. Med. Chem., 2019, 182, 111635.
[http://dx.doi.org/10.1016/j.ejmech.2019.111635] [PMID: 31493744]
[39]
Ju, H.; Xiu, S.; Ding, X.; Shang, M.; Jia, R.; Huang, B.; Zhan, P.; Liu, X. Discovery of novel 1,2,3-triazole oseltamivir derivatives as potent influenza neuraminidase inhibitors targeting the 430-cavity. Eur. J. Med. Chem., 2020, 187, 111940.
[http://dx.doi.org/10.1016/j.ejmech.2019.111940] [PMID: 31835169]
[40]
Cui, M.Y.; Nie, J.X.; Yan, Z.Z.; Xiao, M.W.; Lin, D.; Ye, J.; Hu, A.X. Design, synthesis, bioactivity, and DFT calculation of 2-thiazolyl-hydrazone derivatives as influenza neuraminidase inhibitors. Med. Chem. Res., 2019, 28(7), 938-947.
[http://dx.doi.org/10.1007/s00044-019-02343-3]
[41]
Hu, Y.; Chen, B.; Lei, Z.; Zhao, H.; Zhu, H.; Quan, P.; Tian, Y. Synthesis and biological evaluation of nh2-sulfonyl oseltamivir analogues as influenza neuraminidase inhibitors. Molecules, 2019, 24(11), 2176.
[http://dx.doi.org/10.3390/molecules24112176] [PMID: 31185617]
[42]
Yu, Y.; Qin, H.J.; Shi, X.X.; Song, J.Q.; Zhou, J.P.; Yu, P.; Fan, Z.C.; Zhong, M.; Yang, Y. Thiosialoside-decorated polymers use a two-step mechanism to inhibit both early and late stages of influenza virus infection. Eur. J. Med. Chem., 2020, 199, 112357.
[http://dx.doi.org/10.1016/j.ejmech.2020.112357] [PMID: 32428793]
[43]
Zhong, Z.J.; Cheng, L.P.; Pang, W.; Zheng, X.S.; Fu, S.K. Design, synthesis and biological evaluation of dihydrofurocoumarin derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem. Lett., 2021, 37, 127839.
[http://dx.doi.org/10.1016/j.bmcl.2021.127839] [PMID: 33556571]
[44]
Xiao, M.; Xu, L.; Lin, D.; Lian, W.; Cui, M.; Zhang, M.; Yan, X.; Li, S.; Zhao, J.; Ye, J.; Liu, A.; Hu, A. Design, synthesis, and bioassay of 4-thiazolinone derivatives as influenza neuraminidase inhibitors. Eur. J. Med. Chem., 2021, 213, 113161.
[http://dx.doi.org/10.1016/j.ejmech.2021.113161] [PMID: 33540229]
[45]
Ye, J.; Lin, L.; Xu, J.; Chan, P.K.; Yang, X.; Ma, C. Design, synthesis, biological evaluation and In silico studies of pyrazole-based nh2-acyl oseltamivir analogues as potent neuraminidase inhibitors. Pharmaceuticals, 2021, 14(4), 371.
[http://dx.doi.org/10.3390/ph14040371] [PMID: 33923858]
[46]
Yu, W.; Ping Cheng, L. Pang, W.; Ling Guo, L. Design, synthesis and biological evaluation of novel 1, 3, 4-oxadiazole derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem., 2022, 57, 116647.
[http://dx.doi.org/10.1016/j.bmc.2022.116647] [PMID: 35121400]
[47]
Shi, L.; Zhang, X.Y.; Cheng, L.P. Design, synthesis and biological evaluation of 1,3,4-triazole-3-acetamide derivatives as potent neuraminidase inhibitors. Bioorg. Med. Chem. Lett., 2022, 61, 128590.
[http://dx.doi.org/10.1016/j.bmcl.2022.128590] [PMID: 35108623]
[48]
Zhang, X.Y.; Cheng, L.P.; Zhong, Z.J.; Pang, W.; Song, X. Design, synthesis and biological evaluation of oxalamide derivatives as potent neuraminidase inhibitors. New J. Chem., 2022, 46, 13533-13539.
[http://dx.doi.org/10.1039/D2NJ00726F]
[49]
Wang, K.; Lei, Z.; Zhao, L.; Chen, B.; Yang, F.; Liu, K.; Zhu, H.; Zhao, H.; Cao, R.; Zhang, K.; Tian, Y. Design, synthesis and biological evaluation of oseltamivir derivatives containing pyridyl group as potent inhibitors of neuraminidase for influenza A. Eur. J. Med. Chem., 2020, 185, 111841.
[http://dx.doi.org/10.1016/j.ejmech.2019.111841] [PMID: 31708183]
[50]
Li, M.; Cheng, L.P.; Pang, W.; Zhong, Z.J.; Guo, L.L. Design, synthesis, and biological evaluation of novel acylhydrazone derivatives as potent neuraminidase inhibitors. ACS Med. Chem. Lett., 2020, 11(9), 1745-1750.
[http://dx.doi.org/10.1021/acsmedchemlett.0c00313] [PMID: 32944142]
[51]
(a) Walther, T.; Karamanska, R.; Chan, R.W.Y.; Chan, M.C.W.; Jia, N.; Air, G.; Hopton, C.; Wong, M.P.; Dell, A.; Malik Peiris, J.S.; Haslam, S.M.; Nicholls, J.M. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog., 2013, 9, e1003223.
[http://dx.doi.org/10.1371/journal.pap.1003223];
(b) Roy, A.; Byrne, S.; Sarangi, N.K.; Murphy, P.V.; Keyes, T.E. A cell free biomembrane platform for multimodal study of influenza virus hemagglutinin and for evaluation of entry-inhibitors against hemagglutinin. Front. Mol. Sci., 2022, 9, 1017338.
[http://dx.doi.org/10.3389/fmolb.2022.1017338]
[52]
Vanderlinden, E. Göktaş F.; Cesur, Z.; Froeyen, M.; Reed, M.L.; Russell, C.J.; Cesur, N.; Naesens, L. Novel inhibitors of influenza virus fusion: Structure-activity relationship and interaction with the viral hemagglutinin. J. Virol., 2010, 84(9), 4277-4288.
[http://dx.doi.org/10.1128/JVI.02325-09] [PMID: 20181685]
[53]
Basu, A.; Antanasijevic, A.; Wang, M.; Li, B.; Mills, D.M.; Ames, J.A.; Nash, P.J.; Williams, J.D.; Peet, N.P.; Moir, D.T.; Prichard, M.N.; Keith, K.A.; Barnard, D.L.; Caffrey, M.; Rong, L.; Bowlin, T.L. New small molecule entry inhibitors targeting hemagglutinin-mediated influenza a virus fusion. J. Virol., 2014, 88(3), 1447-1460.
[http://dx.doi.org/10.1128/JVI.01225-13] [PMID: 24198411]
[54]
Zhu, Z.; Yao, Z.; Shen, X.; Chen, Z.; Liu, X.; Parquette, J.R.; Liu, S. Oligothiophene compounds inhibit the membrane fusion between H5N1 avian influenza virus and the endosome of host cell. Eur. J. Med. Chem., 2017, 130, 185-194.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.040] [PMID: 28246043]
[55]
Torres, F.; Brucker, N.; Andrade, S.; Kawano, D.; Garcia, S.; Poser, G.; Eifler-Lima, V. New insights into the chemistry and antioxidant activity of coumarins. Curr. Top. Med. Chem., 2014, 14(22), 2600-2623.
[http://dx.doi.org/10.2174/1568026614666141203144551] [PMID: 25478878]
[56]
Hassan, M.Z.; Osman, H.; Ali, M.A.; Ahsan, M. Therapeutic potential of coumarins as antiviral agents. Eur. J. Med. Chem., 2016, 123, 236-255.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.056]
[57]
Khomenko, T.M.; Zarubaev, V.V.; Orshanskaya, I.R.; Kadyrova, R.A.; Sannikova, V.A.; Korchagina, D.V.; Volcho, K.P.; Salakhutdinov, N.F. Anti-influenza activity of monoterpene-containing substituted coumarins. Bioorg. Med. Chem. Lett., 2017, 27, 2920-2925.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.091] [PMID: 28501512]
[58]
Salakhutdinov, N.F.; Volcho, K.P.; Yarovaya, O.I. Monoterpenes as a renewable source of biologically active compounds. Pure Appl. Chem., 2017, 89(8), 1105-1117.
[http://dx.doi.org/10.1515/pac-2017-0109]
[59]
Ilyina, I.V.; Zarubaev, V.V.; Lavrentieva, I.N.; Shtro, A.A.; Esaulkova, I.L.; Korchagina, D.V.; Borisevich, S.S.; Volcho, K.P.; Salakhutdinov, N.F. Highly potent activity of isopulegol-derived substituted octahydro-2-H-chromen-4-ols against influenza A and B viruses. Bioorg. Med. Chem. Lett., 2018, 28(11), 2061-2067.
[http://dx.doi.org/10.1016/j.bmcl.2018.04.057] [PMID: 29716780]
[60]
Song, G.; Shen, X.; Li, S.; Li, Y.; Liu, Y.; Zheng, Y.; Lin, R.; Fan, J.; Ye, H.; Liu, S. Structure–activity relationships of 3-O-β-chacotriosyl ursolic acid derivatives as novel H5N1 entry inhibitors. Eur. J. Med. Chem., 2015, 93, 431-442.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.029] [PMID: 25728024]
[61]
Liao, Y.; Chen, L.; Li, S.; Cui, Z.; Lei, Z.; Li, H.; Liu, S.; Song, G. Structure-aided optimization of 3-O-β-chacotriosyl ursolic acid as novel H5N1 entry inhibitors with high selective index. Bioorg. Med. Chem., 2019, 27(18), 4048-4058.
[http://dx.doi.org/10.1016/j.bmc.2019.07.028] [PMID: 31350154]
[62]
Walther, T.; Karamanska, R.; Chan, R.W.Y.; Chan, M.C.W.; Jia, N.; Air, G.; Hopton, C.; Wong, M.P.; Dell, A.; Malik Peiris, J.S.; Haslam, S.M.; Nicholls, J.M. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog., 2013, 9(3), e1003223.
[http://dx.doi.org/10.1371/journal.ppat.1003223] [PMID: 23516363]
[63]
Bhatia, S.; Lauster, D.; Bardua, M.; Ludwig, K.; Angioletti-Uberti, S.; Popp, N.; Hoffmann, U.; Paulus, F.; Budt, M.; Stadtmüller, M.; Wolff, T.; Hamann, A.; Böttcher, C.; Herrmann, A.; Haag, R. Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo. Biomaterials, 2017, 138, 22-34.
[http://dx.doi.org/10.1016/j.biomaterials.2017.05.028] [PMID: 28550754]
[64]
Dong, J.; Chen, S.; Li, R.; Cui, W.; Jiang, H.; Ling, Y.; Yang, Z.; Hu, W. Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus. Eur. J. Med. Chem., 2016, 108, 605-615.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.013] [PMID: 26722757]
[65]
Gordon, N.A.; McGuire, K.L.; Wallentine, S.K.; Mohl, G.A.; Lynch, J.D.; Harrison, R.G.; Busath, D.D. Divalent copper complexes as influenza A M2 inhibitors. Antiviral Res., 2017, 147, 100-106.
[http://dx.doi.org/10.1016/j.antiviral.2017.10.009] [PMID: 29032206]
[66]
Suslov, E.; Zarubaev, V.V.; Slita, A.V.; Ponomarev, K.; Korchagina, D.; Ayine-Tora, D.M.; Reynisson, J.; Volcho, K.; Salakhutdinov, N. Anti-influenza activity of diazaadamantanes combined with monoterpene moieties. Bioorg. Med. Chem. Lett., 2017, 27(19), 4531-4535.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.062] [PMID: 28886889]
[67]
Wu, S.; Huang, J.; Gazzarrini, S.; He, S.; Chen, L.; Li, J.; Xing, L.; Li, C.; Chen, L.; Neochoritis, C.G.; Liao, G.P.; Zhou, H.; Dömling, A.; Moroni, A.; Wang, W. Isocyanides as influenza a virus subtype H5N1 wild-type m2 channel inhibitors. ChemMedChem, 2015, 10(11), 1837-1845.
[http://dx.doi.org/10.1002/cmdc.201500318] [PMID: 26506405]
[68]
Drakopoulos, A.; Tzitzoglaki, C.; McGuire, K.; Hoffmann, A.; Konstantinidi, A.; Kolokouris, D.; Ma, C.; Freudenberger, K.; Hutterer, J.; Gauglitz, G.; Wang, J.; Schmidtke, M.; Busath, D.D.; Kolocouris, A. Unraveling the binding, proton blockage, and inhibition of influenza M2 wt and S31N by rimantadine variants. ACS Med. Chem. Lett., 2018, 9, 198-203.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00458] [PMID: 29541360]
[69]
Wang, J.; Ma, C.; Wang, J.; Jo, H.; Canturk, B.; Fiorin, G.; Pinto, L.H.; Lamb, R.A.; Klein, M.L.; DeGrado, W.F. 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. Med. Chem., 2013, 56(7), 2804-2812.
[http://dx.doi.org/10.1021/jm301538e] [PMID: 23437766]
[70]
Li, F.; Ma, C.; DeGrado, W.F.; Wang, J. Discovery of highly potent inhibitors targeting the predominant drug-resistant S31N Mutant of the influenza a virus M2 proton channel. J. Med. Chem., 2016, 59(3), 1207-1216.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01910] [PMID: 26771709]
[71]
Li, F.; Hu, Y.; Wang, Y.; Ma, C.; Wang, J. Expeditious lead optimization of isoxazole-containing influenza a virus m2-s31n inhibitors using the suzuki–miyaura cross-coupling reaction. J. Med. Chem., 2017, 60(4), 1580-1590.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01852] [PMID: 28182419]
[72]
Peng, S. Progression of antiviral agents targeting viral polymerases. Molecules, 2022, 27(21), 7370.
[http://dx.doi.org/10.3390/molecules27217370]
[73]
Clark, M.P.; Ledeboer, M.W.; Davies, I.; Byrn, R.A.; Jones, S.M.; Perola, E.; Tsai, A.; Jacobs, M.; Nti-Addae, K.; Bandarage, U.K.; Boyd, M.J.; Bethiel, R.S.; Court, J.J.; Deng, H.; Duffy, J.P.; Dorsch, W.A.; Farmer, L.J.; Gao, H.; Gu, W.; Jackson, K.; Jacobs, D.H.; Kennedy, J.M.; Ledford, B.; Liang, J.; Maltais, F.; Murcko, M.; Wang, T.; Wannamaker, M.W.; Bennett, H.B.; Leeman, J.R.; McNeil, C.; Taylor, W.P.; Memmott, C.; Jiang, M.; Rijnbrand, R.; Bral, C.; Germann, U.; Nezami, A.; Zhang, Y.; Salituro, F.G.; Bennani, Y.L.; Charifson, P.S. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J. Med. Chem., 2014, 57(15), 6668-6678.
[http://dx.doi.org/10.1021/jm5007275] [PMID: 25019388]
[74]
Bandarage, U.K.; Clark, M.P.; Perola, E.; Gao, H.; Jacobs, M.D.; Tsai, A.; Gillespie, J.; Kennedy, J.M.; Maltais, F.; Ledeboer, M.W.; Davies, I.; Gu, W.; Byrn, R.A.; Addae, R.A.; Bennett, H.; Leeman, J.R.; Jones, S.M.; O’Brien, C.; Memmott, C.; Bennani, Y.; Charifson, P.S. Novel 2-substituted 7-azaindole and 7-azaindazole analogues as potential antiviral agents for the treatment of influenza. ACS Med. Chem. Lett., 2017, 8, 261-265.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00487] [PMID: 28197323]
[75]
Massari, S.; Desantis, J.; Nannetti, G.; Sabatini, S.; Tortorella, S.; Goracci, L.; Cecchetti, V.; Loregian, A.; Tabarrini, O. Efficient and regioselective one-step synthesis of 7-aryl-5-methyl- and 5-aryl-7-methyl-2-amino-[1,2,4]triazolo[1,5-a]pyrimidine derivatives. Org. Biomol. Chem., 2017, 15(37), 7944-7955.
[http://dx.doi.org/10.1039/C7OB02085F]
[76]
Pismataro, M.C.; Felicetti, T.; Bertagnin, C.; Nizi, M.G.; Bonomini, A.; Barreca, M.L.; Cecchetti, V.; Jochmans, D.; De Jonghe, S.; Neyts, J.; Loregian, A.; Tabarrini, O.; Massari, S. 2,4-Triazolo[1,5-a]pyrimidines: Efficient one-step synthesis and functionalization as influenza polymerase PA-PB1 interaction disruptors. Eur. J. Med. Chem., 2021, 221, 113494.
[http://dx.doi.org/10.1016/j.ejmech.2021.113494]
[77]
Kim, C.U.; Jeong, Y.J.; Lee, P. Extracellular nucleoprotein exacerbates influenza virus pathogenesis by activating Toll-like receptor 4 and the NLRP3 inflammasome. Cell. Mol. Immunol., 2022, 19(6), 715-725.
[http://dx.doi.org/10.1038/s41423-022-00862-5]
[78]
Rogolino, D.; Naesens, L.; Bartoli, J.; Carcelli, M.; De Luca, L.; Pelosi, G.; Stokes, R.W.; Van Berwaer, R.; Vittorio, S.; Stevaert, A.; Cohen, S.M. Exploration of the 2,3-dihydroisoindole pharmacophore for inhibition of the influenza virus PA endonuclease. Bioorg. Chem., 2021, 116, 105388.
[http://dx.doi.org/10.1016/j.bioorg.2021.105388] [PMID: 34670331]
[79]
Credille, C.V.; Dick, B.L.; Morrison, C.N.; Stokes, R.W.; Adamek, R.N.; Wu, N.C.; Wilson, I.A.; Cohen, S.M. Structure-activity relationships in metal-binding pharmacophores for influenza endonuclease. J. Med. Chem., 2018, 61, 10206-10217.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01363] [PMID: 30351002]
[80]
Jacobsen, J.A.; Fullagar, J.L.; Miller, M.T.; Cohen, S.M. Identifying chelators for metalloprotein inhibitors using a fragment-based approach. J. Med. Chem., 2011, 54(2), 591-602.
[http://dx.doi.org/10.1021/jm101266s]
[81]
Credille, C.V.; Morrison, C.N.; Stokes, R.W.; Dick, B.L.; Feng, Y.; Sun, J.; Chen, Y.; Cohen, S.M. SAR exploration of tight-binding inhibitors of influenza virus PA endonuclease. J. Med. Chem., 2019, 62(21), 9438-9449.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00747] [PMID: 31536340]
[82]
Sethy, B.; Hsieh, C.F.; Lin, T.J.; Hu, P.Y.; Chen, Y.L.; Lin, C.Y.; Tseng, S-N.; Horng, J.T.; Hsieh, P.W. Design, synthesis, and biological evaluation of itaconic acid derivatives as potential anti-influenza agents. J. Med. Chem., 2019, 62(5), 2390-2403.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01683]
[83]
Szűcs, Z.; Csávás, M.; Rőth, E.; Borbás, A.; Batta, G.; Perret, F.; Ostorházi, E.; Szatmári, R.; Vanderlinden, E.; Naesens, L.; Herczegh, P. Synthesis and biological evaluation of lipophilic teicoplanin pseudoaglycon derivatives containing a substituted triazole function. J. Antibiot., 2017, 70(2), 152-157.
[http://dx.doi.org/10.1038/ja.2016.80] [PMID: 27353163]
[84]
Pintér, G.; Batta, G.; Kéki, S.; Mándi, A.; Komáromi, I.; Takács-Novák, K.; Sztaricskai, F.; Röth, E.; Ostorházi, E.; Rozgonyi, F.; Naesens, L.; Herczegh, P. Diazo transfer-click reaction route to new, lipophilic teicoplanin and ristocetin aglycon derivatives with high antibacterial and anti-influenza virus activity: An aggregation and receptor binding study. J. Med. Chem., 2009, 52(19), 6053-6061.
[http://dx.doi.org/10.1021/jm900950d] [PMID: 19791806]
[85]
a) Wintachai, P.K.; Lee, R.C.; Ramphan, S.; Kuadkitkan, A.; Wikan, N.; Ubol, S.; Roytrakul, S.; Chu, J.J.; Smith, D.R. Activity of andrographolide against chikungunya virus infection. Sci. Rep., 2020, 5, 14179.
[http://dx.doi.org/10.1038/srep14179];
b) Gupta, S.; Mishra, K.P.; Ganju, L. Broad-spectrum antiviral properties of andrographolide. Arch. Virol., 2017, 162, 611-623.
[http://dx.doi.org/10.1007/s00705-016-3166-3];
c) Majumdar, M.; Misra, T.K.; Roy, D.N.; Braz, J. In vitro anti-biofilm activity of 14-deoxy-11,12-didehydroandro-] grapholide from Andrographis paniculata against Pseudomonas aeruginosa. Microbiol., 2020, 51, 15-27.
[http://dx.doi.org/10.1007/s42770-019-00169-0];
d) Zhang, H.; Li, S.; Si, Y. XU, H. Andrographolide and its derivatives: Current achievements and future perspectives. Eur. J. Med. Chem., 2021, 224, 113710.
[http://dx.doi.org/10.1016/j.ejmech.2021.113710]
[86]
Yuan, L.; Zhang, C.; Sun, H.; Liu, Q.; Huang, J.; Sheng, L.; Lin, B.; Wang, J.; Chen, L. The semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives. Bioorg. Med. Chem. Lett., 2016, 26(3), 769-773.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.100] [PMID: 26791013]
[87]
Ivanova, A.E.; Burgart, Y.V.; Saloutin, V.I. Non-natural nucleosides bearing 4-aryldiazenylpyrazole aglycone. Mendeleev Commun., 2016, 26(2), 106-108.
[http://dx.doi.org/10.1016/j.mencom.2016.03.006];
Ivanova, A.E.; Burgart, Y.V.; Saloutin, V.I.; Orshanskaya, Y.R.; Zarubaev, V.V. β-d-Ribofuranosyl substituted polyfluoroalkylpyrazoles and their activity against the influenza virus. Mendeleev Commun., 2018, 28(1), 52-54.
[http://dx.doi.org/10.1016/j.mencom.2018.01.017]
[88]
Chiacchio, U.; Gumina, G.; Rescifina, A.; Romeo, R.; Uccella, N.; Casuscelli, F.; Piperno, A.; Romeo, G. Modified dideoxynucleosides: Synthesis of 2′-N-alkyl-3′-hydroxyalkyl-1′,2′-isoxazolidinyl thymidine and 5-fluorouridine derivatives. Tetrahedron, 1996, 52(26), 8889-8898.
[http://dx.doi.org/10.1016/0040-4020(96)00437-1]
[89]
Li, G.; Obul, M.; Zhao, J.; Liu, G.; Lu, W.; Aisa, H.A. Novel amides modified rupestonic acid derivatives as anti-influenza virus reagents. Bioorg. Med. Chem. Lett., 2019, 29(19), 126605.
[http://dx.doi.org/10.1016/j.bmcl.2019.08.009] [PMID: 31439378]
[90]
Lamuta, A.; Naesens, L.; Liekens, S.; Lillsunde, K-E.; Tammela, P.; Kikelja, D. Tomašič T. Anti-influenza virus activity of benzo[d]thiazoles that target heat shock protein 90. Bioorg. Chem., 2020, 98, 103733.
[http://dx.doi.org/10.1016/j.bioorg.2020.103733]
[91]
Gjorgjieva, M.; Tomašič, T.; Barančokova, M.; Katsamakas, S.; Ilaš, J.; Tammela, P.; Peterlin Mašič, L.; Kikelj, D. Discovery of benzothiazole scaffold-based dna gyrase b inhibitors. J. Med. Chem., 2016, 59(19), 8941-8954.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00864] [PMID: 27541007]
[92]
Apaydın, Ç.B.; Tansuyu, M.; Cesur, Z.; Naesens, L.; Göktaş, F. Design, synthesis and anti-influenza virus activity of furan-substituted spirothiazolidinones. Bioorg. Chem., 2021, 112, 104958.
[http://dx.doi.org/10.1016/j.bioorg.2021.104958] [PMID: 33979734]
[93]
Hussain, M.; Galvin, H.; Haw, T.Y.; Nutsford, A.; Husain, M. Drug resistance in influenza A virus: The epidemiology and management. Infect. Drug Resist., 2017, 10, 121-134.
[http://dx.doi.org/10.2147/IDR.S105473] [PMID: 28458567]
[94]
Zarubaev, V.V.; Pushkina, E.A.; Borisevich, S.S.; Galochkina, A.V.; Garshinina, A.V.; Shtro, A.A.; Egorova, A.A.; Sokolova, A.S.; Khursan, S.L.; Yarovaya, O.I.; Salakhutdinov, N.F. Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity. Virology, 2018, 524, 69-77.
[http://dx.doi.org/10.1016/j.virol.2018.08.011] [PMID: 30165308]
[95]
Zarubaev, V.V.; Garshinina, A.V.; Volobueva, A.S.; Slita, A.V.; Yarovaya, O.I.; Bykov, V.V.; Leonov, K.A.; Motov, V.S.; Khazanov, V.A.; Salakhutdinov, N.F. Optimization of application schedule of camphecene, a novel anti-influenza compound, based on its pharmacokinetic characteristics. Fundam. Clin. Pharmacol., 2022, 36(3), 518-525.
[http://dx.doi.org/10.1111/fcp.12750] [PMID: 34984730]
[96]
Wu, Q.; Wang, W.; Dai, X.; Wang, Z.; Shen, Z.; Ying, H.; Yu, C. Chemical compositions and anti-influenza activities of essential oils from Mosla dianthera. J. Ethnopharmacol., 2012, 139(2), 668-671.
[http://dx.doi.org/10.1016/j.jep.2011.11.056] [PMID: 22193174]
[97]
Madia, V.N.; Toscanelli, W.; De Vita, D.; De Angelis, M.; Messore, A.; Longo, D.; Scipione, L.; Tudino, V.; Diodata D’, A.; Di Santo, R.; Garzoli, S.; Stringaro, A.; Colone, M.; Marchetti, M.; Superti, F.; Nencioni, L.; Costi, R. Ultrastructural damages to H1N1 Influenza virus caused by vapor essential oils. Molecules, 2022, 27, 3718.
[http://dx.doi.org/10.3390/molecules27123718] [PMID: 35744845]

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