Generic placeholder image

Current Medicinal Chemistry

Author(s): Hao Lin, Srinivasulu Cherukupalli, Da Feng, Shenghua Gao*, Dongwei Kang*, Peng Zhan* and Xinyong Liu*

DOI: 10.2174/0929867328666210420103021

DownloadDownload PDF Flyer Cite As
SARS-CoV-2 Entry Inhibitors Targeting Virus-ACE2 or Virus-TMPRSS2 Interactions

Page: [682 - 699] Pages: 18

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

COVID-19 is an infectious disease caused by SARS-CoV-2. The life cycle of SARS-CoV-2 includes the entry into the target cells, replicase translation, replicating and transcribing genomes, translating structural proteins, assembling and releasing new virions. Entering host cells is a crucial stage in the early life cycle of the virus, and blocking this stage can effectively prevent virus infection. SARS enters the target cells mediated by the interaction between the viral S protein and the target cell surface receptor angiotensin- converting enzyme 2 (ACE2), as well as the cleavage effect of a type-II transmembrane serine protease (TMPRSS2) on the S protein. Therefore, the ACE2 receptor and TMPRSS2 are important targets for SARS-CoV-2 entry inhibitors. Herein, we provide a concise report/information on drugs with potential therapeutic value targeting virus-ACE2 or virus-TMPRSS2 interactions to provide a reference for the design and discovery of potential entry inhibitors against SARS-CoV-2.

Keywords: SARS-CoV-2, COVID-19, spike protein, angiotensin-converting enzyme 2, transmembrane protease, serine 2, drug design.

[1]
Alexander, E. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 2020, 5(4), 536-544.
[http://dx.doi.org/10.1038/s41564-020-0695-z] [PMID: 32123347]
[2]
Masters, P.S. The molecular biology of coronaviruses. Adv. Virus Res., 2006, 66, 193-292.
[http://dx.doi.org/10.1016/S0065-3527(06)66005-3] [PMID: 16877062]
[3]
Teissier, E.; Penin, F.; Pécheur, E.I. Targeting cell entry of enveloped viruses as an antiviral strategy. Molecules, 2010, 16(1), 221-250.
[http://dx.doi.org/10.3390/molecules16010221] [PMID: 21193846]
[4]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[5]
Hulswit, R.J.; de Haan, C.A.; Bosch, B.J. Coronavirus spike protein and tropism changes. Adv. Virus Res., 2016, 96, 29-57.
[http://dx.doi.org/10.1016/bs.aivir.2016.08.004] [PMID: 27712627]
[6]
Li, F. Structure, function, and evolution of coronavirus spike proteins. Annu. Rev. Virol., 2016, 3(1), 237-261.
[http://dx.doi.org/10.1146/annurev-virology-110615-042301] [PMID: 27578435]
[7]
Fung, T.S.; Liu, D.X. Human coronavirus: host-pathogen interaction. Annu. Rev. Microbiol., 2019, 73, 529-557.
[http://dx.doi.org/10.1146/annurev-micro-020518-115759] [PMID: 31226023]
[8]
Bosch, B.J.; van der Zee, R.; de Haan, C.A.M.; Rottier, P.J.M. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J. Virol., 2003, 77(16), 8801-8811.
[http://dx.doi.org/10.1128/JVI.77.16.8801-8811.2003] [PMID: 12885899]
[9]
Walls, A.C.; Tortorici, M.A.; Snijder, J.; Xiong, X.; Bosch, B.J.; Rey, F.A.; Veesler, D. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. USA, 2017, 114(42), 11157-11162.
[http://dx.doi.org/10.1073/pnas.1708727114] [PMID: 29073020]
[10]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[11]
Bao, L.; Deng, W.; Huang, B.; Gao, H.; Liu, J.; Ren, L.; Wei, Q.; Yu, P.; Xu, Y.; Qi, F.; Qu, Y.; Li, F.; Lv, Q.; Wang, W.; Xue, J.; Gong, S.; Liu, M.; Wang, G.; Wang, S.; Song, Z.; Zhao, L.; Liu, P.; Zhao, L.; Ye, F.; Wang, H.; Zhou, W.; Zhu, N.; Zhen, W.; Yu, H.; Zhang, X.; Guo, L.; Chen, L.; Wang, C.; Wang, Y.; Wang, X.; Xiao, Y.; Sun, Q.; Liu, H.; Zhu, F.; Ma, C.; Yan, L.; Yang, M.; Han, J.; Xu, W.; Tan, W.; Peng, X.; Jin, Q.; Wu, G.; Qin, C. The pathogenicity of SARS- CoV-2 in hACE2 transgenic mice. Nature, 2020, 583(7818), 830-833.
[http://dx.doi.org/10.1038/s41586-020-2312-y] [PMID: 32380511]
[12]
Li, J.; Zhan, P.; Liu, X. Targeting the entry step of SARS- CoV-2: a promising therapeutic approach. Signal Transduct. Target. Ther., 2020, 5(1), 98.
[http://dx.doi.org/10.1038/s41392-020-0195-x] [PMID: 32555145]
[13]
Wrapp, D.; Wang, N.; Corbett, K.S.; Goldsmith, J.A.; Hsieh, C.L.; Abiona, O.; Graham, B.S.; McLellan, J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020, 367(6483), 1260-1263.
[http://dx.doi.org/10.1126/science.abb2507] [PMID: 32075877]
[14]
Glowacka, I.; Bertram, S.; Müller, M.A.; Allen, P.; Soilleux, E.; Pfefferle, S.; Steffen, I.; Tsegaye, T.S.; He, Y.; Gnirss, K.; Niemeyer, D.; Schneider, H.; Drosten, C.; Pöhlmann, S. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J. Virol., 2011, 85(9), 4122-4134.
[http://dx.doi.org/10.1128/JVI.02232-10] [PMID: 21325420]
[15]
Matsuyama, S.; Nagata, N.; Shirato, K.; Kawase, M.; Takeda, M.; Taguchi, F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J. Virol., 2010, 84(24), 12658-12664.
[http://dx.doi.org/10.1128/JVI.01542-10] [PMID: 20926566]
[16]
Shulla, A.; Heald-Sargent, T.; Subramanya, G.; Zhao, J.; Perlman, S.; Gallagher, T. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J. Virol., 2011, 85(2), 873-882.
[http://dx.doi.org/10.1128/JVI.02062-10] [PMID: 21068237]
[17]
Ou, X.; Liu, Y.; Lei, X.; Li, P.; Mi, D.; Ren, L.; Guo, L.; Guo, R.; Chen, T.; Hu, J.; Xiang, Z.; Mu, Z.; Chen, X.; Chen, J.; Hu, K.; Jin, Q.; Wang, J.; Qian, Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun., 2020, 11(1), 1620.
[http://dx.doi.org/10.1038/s41467-020-15562-9] [PMID: 32221306]
[18]
Xiu, S.; Dick, A.; Ju, H.; Mirzaie, S.; Abdi, F.; Cocklin, S.; Zhan, P.; Liu, X. Inhibitors of SARS-CoV-2 entry: current and future opportunities. J. Med. Chem., 2020, 63(21), 12256-12274.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00502] [PMID: 32539378]
[19]
Haga, S.; Nagata, N.; Okamura, T.; Yamamoto, N.; Sata, T.; Yamamoto, N.; Sasazuki, T.; Ishizaka, Y. TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. Antiviral Res., 2010, 85(3), 551-555.
[http://dx.doi.org/10.1016/j.antiviral.2009.12.001] [PMID: 19995578]
[20]
Matsuyama, S.; Ujike, M.; Morikawa, S.; Tashiro, M.; Taguchi, F. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc. Natl. Acad. Sci. USA, 2005, 102(35), 12543-12547.
[http://dx.doi.org/10.1073/pnas.0503203102] [PMID: 16116101]
[21]
da Silva, J.S.; Gabriel-Costa, D.; Wang, H.; Ahmad, S.; Sun, X.; Varagic, J.; Sudo, R.T.; Ferrario, C.M.; Dell Italia, L.J.; Sudo, G.Z.; Groban, L. Blunting of cardioprotective actions of estrogen in female rodent heart linked to altered expression of cardiac tissue chymase and ACE2. J. Renin Angiotensin Aldosterone Syst., 2017, 18(3), 1470320317722270.
[http://dx.doi.org/10.1177/1470320317722270] [PMID: 28748720]
[22]
Iwata-Yoshikawa, N.; Okamura, T.; Shimizu, Y.; Hasegawa, H.; Takeda, M.; Nagata, N. TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J. Virol., 2019, 93(6), e01815-18.
[http://dx.doi.org/10.1128/JVI.01815-18] [PMID: 30626688]
[23]
Li, S.R.; Tang, Z.J.; Li, Z.H.; Liu, X. Searching therapeutic strategy of new coronavirus pneumonia from angiotensin-converting enzyme 2: the target of COVID-19 and SARS-CoV. Eur. J. Clin. Microbiol. Infect. Dis., 2020, 39(6), 1021-1026.
[http://dx.doi.org/10.1007/s10096-020-03883-y] [PMID: 32285293]
[24]
Gheblawi, M.; Wang, K.; Viveiros, A.; Nguyen, Q.; Zhong, J.C.; Turner, A.J.; Raizada, M.K.; Grant, M.B.; Oudit, G.Y. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ. Res., 2020, 126(10), 1456-1474.
[http://dx.doi.org/10.1161/CIRCRESAHA.120.317015] [PMID: 32264791]
[25]
Patel, V.B.; Zhong, J.C.; Grant, M.B.; Oudit, G.Y. Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure. Circ. Res., 2016, 118(8), 1313-1326.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.307708] [PMID: 27081112]
[26]
Meirson, T; Bomze, D; Markel, G. Structural basis of SARS-CoV-2 spike protein induced by ACE2. Bioinformatics, 2021, 37(7), 929-936.
[http://dx.doi.org/10.1093/bioinformatics/btaa744]
[27]
Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 2020, 367(6485), 1444-1448.
[http://dx.doi.org/10.1126/science.abb2762] [PMID: 32132184]
[28]
Wan, Y.; Shang, J.; Graham, R.; Baric, R.S.; Li, F. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J. Virol., 2020, 94(7), e120-e127.
[http://dx.doi.org/10.1128/JVI.00127-20] [PMID: 31996437]
[29]
Li, F.; Li, W.; Farzan, M.; Harrison, S.C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 2005, 309(5742), 1864-1868.
[http://dx.doi.org/10.1126/science.1116480] [PMID: 16166518]
[30]
Chen, X.; Wu, Y.; Chen, C.; Gu, Y.; Zhu, C.; Wang, S.; Chen, J.; Zhang, L.; Lv, L.; Zhang, G.; Yuan, Y.; Chai, Y.; Zhu, M.; Wu, C. Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening. Acta Pharm. Sin. B, 2021, 11(1), 222-236.
[PMID: 33072499]
[31]
Batlle, D.; Wysocki, J.; Satchell, K. Soluble angiotensin- converting enzyme 2: a potential approach for coronavirus infection therapy? Clin. Sci. (Lond.), 2020, 134(5), 543-545.
[http://dx.doi.org/10.1042/CS20200163] [PMID: 32167153]
[32]
Monteil, V.; Kwon, H.; Prado, P.; Hagelkrüys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Hurtado Del Pozo, C.; Prosper, F.; Romero, J.P.; Wirnsberger, G.; Zhang, H.; Slutsky, A.S.; Conder, R.; Montserrat, N.; Mirazimi, A.; Penninger, J.M. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell, 2020, 181(4), 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[33]
Sharifkashani, S.; Bafrani, M.A.; Khaboushan, A.S.; Pirzadeh, M.; Kheirandish, A.; Yavarpour Bali, H.; Hessami, A.; Saghazadeh, A.; Rezaei, N. Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting. Eur. J. Pharmacol., 2020, 884, 173455.
[http://dx.doi.org/10.1016/j.ejphar.2020.173455] [PMID: 32745604]
[34]
Han, Y.; Duan, X.; Yang, L.; Benjamin, E. Nilsson- Payant; Pengfei Wang; Fuyu Duan; Xuming Tang; Tomer M. Yaron; Tuo Zhang; Skyler Uhl; Yaron Bram; Chanel Richardson; Jiajun Zhu; Zeping Zhao; David Redmond; Sean Houghton; Duc-Huy T. Nguyen; Dong Xu; Xing Wang; Jose Jessurun; Alain Borczuk; Yaoxing Huang; Jared L. Johnson; Yuru Liu; Jenny Xiang; Hui Wang; Lewis C. Cantley; Benjamin R. TenOever; David D. Ho; Fong Cheng Pan; Todd Evans; Huanhuan Joyce Chen; Robert E. Schwartz; Shuibing Chen. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature, 2021, 589, 270–275.
[35]
Morse, J.S.; Lalonde, T.; Xu, S.; Liu, W.R. Learning from the Past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. ChemBioChem, 2020, 21(5), 730-738.
[http://dx.doi.org/10.1002/cbic.202000047] [PMID: 32022370]
[36]
Bian, J.; Li, Z. Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator. Acta Pharm. Sin. B, 2021, 11(1), 1-12.
[PMID: 33072500]
[37]
Wu, C.; Liu, Y.; Yang, Y.; Zhang, P.; Zhong, W.; Wang, Y.; Wang, Q.; Xu, Y.; Li, M.; Li, X.; Zheng, M.; Chen, L.; Li, H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B, 2020, 10(5), 766-788.
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[38]
Ni, W.; Yang, X.; Yang, D.; Bao, J.; Li, R.; Xiao, Y.; Hou, C.; Wang, H.; Liu, J.; Yang, D.; Xu, Y.; Cao, Z.; Gao, Z. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit. Care, 2020, 24(1), 422.
[http://dx.doi.org/10.1186/s13054-020-03120-0] [PMID: 32660650]
[39]
Fang, L.; Karakiulakis, G.; Roth, M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir. Med., 2020, 8(4), e21.
[http://dx.doi.org/10.1016/S2213-2600(20)30116-8] [PMID: 32171062]
[40]
Li, X.; Liu, Y.; Song, J.; Zhong, J. Increased plasma ACE2 concentration does not mean increased risk of SARS-CoV-2 infection and increased fatality rate of COVID-19. Acta Pharm. Sin. B, 2020, 10(10), 2010-2014.
[http://dx.doi.org/10.1016/j.apsb.2020.09.003] [PMID: 32923317]
[41]
Zhang, X.L.; Li, Z.M.; Ye, J.T.; Lu, J.; Ye, L.L.; Zhang, C.X.; Liu, P.Q.; Duan, D.D. Pharmacological and cardiovascular perspectives on the treatment of COVID-19 with chloroquine derivatives. Acta Pharmacol. Sin., 2020, 41(11), 1377-1386.
[http://dx.doi.org/10.1038/s41401-020-00519-x] [PMID: 32968208]
[42]
Dong, L.; Hu, S.; Gao, J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov. Ther., 2020, 14(1), 58-60.
[http://dx.doi.org/10.5582/ddt.2020.01012] [PMID: 32147628]
[43]
Celı K, I.; Onay-Besı Kcı, A.; Ayhan-Kilcigı L, G. Approach to the mechanism of action of hydroxychloroquine on SARS-CoV-2: a molecular docking study. J. Biomol. Struct. Dyn., 2020, 39(15), 5792-5798.
[http://dx.doi.org/10.1080/07391102.2020.1792993] [PMID: 32677545]
[44]
Yuan, Z.; Pavel, M.A.; Wang, H.; Hansen, S.B. Hydroxychloroquine: mechanism of action inhibiting SARS- CoV2 entry. bioRxiv, 2020, 2020.08.13.250217.
[PMID: 32817933]
[45]
Vincent, M.J.; Bergeron, E.; Benjannet, S.; Erickson, B.R.; Rollin, P.E.; Ksiazek, T.G.; Seidah, N.G.; Nichol, S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J., 2005, 2, 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[46]
Hoffmann, M.; Mösbauer, K.; Hofmann-Winkler, H.; Kaul, A.; Kleine-Weber, H.; Krüger, N.; Gassen, N.C.; Müller, M.A.; Drosten, C.; Pöhlmann, S. Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2. Nature, 2020, 585(7826), 588-590.
[http://dx.doi.org/10.1038/s41586-020-2575-3] [PMID: 32698190]
[47]
Choudhary, S. Yashpal S. Malik; Shailly Tomar. Identification of SARS-CoV-2 cell entry inhibitors by drug repurposing using in silico structure-based virtual screening approach. Front. Immunol., 2020, 11, 1664.
[48]
Panda, P.K.; Arul, M.N.; Patel, P.; Verma, S.K.; Luo, W.; Rubahn, H.G.; Mishra, Y.K.; Suar, M.; Ahuja, R. Structure-based drug designing and immunoinformatics approach for SARS-CoV-2. Sci. Adv., 2020, 11(28), eabb8097.
[http://dx.doi.org/10.1126/sciadv.abb8097] [PMID: 32691011]
[49]
Francisco Wagner, Q. Almeida-Neto; Maria Geysillene Castro Matos; Emanuelle Machado Marinho; Márcia Machado Marinho; Ramon Róseo Paula Pessoa Bezerra De Menezes; Tiago Lima Sampaio; Paulo Nogueira Bandeira; Carla Freire Celedonio Fernandes; Alexandre Magno Rodrigues Teixeira; Emmanuel Silva Marinho; Pedro de Lima-Neto; Hélcio Silva Dos Santos. In silico study of the potential interactions of 4′-acetamidechalcones with protein targets in SARS-CoV-2. Biochem. Biophys. Res. Commun., 2021, 537, 71-77.
[50]
Xia, S.; Zhu, Y.; Liu, M.; Lan, Q.; Xu, W.; Wu, Y.; Ying, T.; Liu, S.; Shi, Z.; Jiang, S.; Lu, L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol., 2020, 17(7), 765-767.
[http://dx.doi.org/10.1038/s41423-020-0374-2] [PMID: 32047258]
[51]
Dwight, L. McKee; Ariane Sternberg; Ulrike Stange; Stefan Laufer; Cord Naujokat. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol. Res., 2020, 157, 104859.
[http://dx.doi.org/10.1016/j.phrs.2020.104859]
[52]
Bhattarai, Apurba; Pawnikar, Shristi; Miao, Yinglong Mechanism of ligand recognition by human ACE2 receptor. bioRxiv: the preprint server for biology, 2020, 2020. 10.30.362749.
[http://dx.doi.org/10.1101/2020.10.30.362749] [PMID: 33140043]
[53]
Kawase, M.; Shirato, K.; van der Hoek, L.; Taguchi, F.; Matsuyama, S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J. Virol., 2012, 86(12), 6537-6545.
[http://dx.doi.org/10.1128/JVI.00094-12] [PMID: 22496216]
[54]
Hoffmann, M.; Simon, Schroeder; Hannah, Kleine-Weber; Marcel A., Müller; Christian, Drosten; Stefan, Pöhlmann. Nafamostat mesylate blocks activation of SARS-CoV-2: new treatment option for COVID-19. Antimicrob Agents Ch, 2020, 64(6), e00754-20.
[55]
Yamamoto, M.; Kiso, M.; Sakai-Tagawa, Y.; Iwatsuki-Horimoto, K.; Imai, M.; Takeda, M.; Kinoshita, N.; Ohmagari, N.; Gohda, J.; Semba, K.; Matsuda, Z.; Kawaguchi, Y.; Kawaoka, Y.; Inoue, J.I. The anticoagulant nafamostat potently inhibits SARS-CoV-2 S protein-mediated fusion in a cell fusion assay system and viral infection in vitro in a cell-type-dependent manner. Viruses, 2020, 12(6), 629.
[http://dx.doi.org/10.3390/v12060629] [PMID: 32532094]
[56]
Jared, M. Lucas; Cynthia Heinlein; Tom Kim; Susana A. Hernandez; Muzdah S. Malik; Lawrence D. True; Colm Morrissey; Eva Corey; Bruce Montgomery; Elahe Mostaghel; Nigel Clegg; Ilsa Coleman; Christopher M. Brown; Eric L. Schneider; Charles Craik; Julian A. Simon; Antonio Bedalov; Peter S. Nelson. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov., 2014, 4(11), 1310-25.
[57]
Cannalire, R.; Stefanelli, I.; Cerchia, C.; Beccari, A.R.; Pelliccia, S.; Summa, V. SARS-CoV-2 entry inhibitors: Small molecules and peptides targeting virus or host cells. Int. J. Mol. Sci., 2020, 21(16), E5707.
[http://dx.doi.org/10.3390/ijms21165707] [PMID: 32784899]
[58]
Shen, L.W.; Qian, M.Q.; Yu, K.; Narva, S.; Yu, F.; Wu, Y.L.; Zhang, W. Inhibition of Influenza A virus propagation by benzoselenoxanthenes stabilizing TMPRSS2 Gene G-quadruplex and hence down-regulating TMPRSS2 expression. Sci. Rep., 2020, 10(1), 7635.
[http://dx.doi.org/10.1038/s41598-020-64368-8] [PMID: 32376987]
[59]
Mikkonen, L.; Pihlajamaa, P.; Sahu, B.; Zhang, F.P.; Jänne, O.A. Androgen receptor and androgen-dependent gene expression in lung. Mol. Cell. Endocrinol., 2010, 317(1-2), 14-24.
[http://dx.doi.org/10.1016/j.mce.2009.12.022] [PMID: 20035825]
[60]
Stopsack, K.H.; Mucci, L.A.; Antonarakis, E.S.; Nelson, P.S.; Kantoff, P.W. TMPRSS2 and COVID-19: serendipity or opportunity for intervention? Cancer Discov., 2020, 10(6), 779-782.
[http://dx.doi.org/10.1158/2159-8290.CD-20-0451] [PMID: 32276929]
[61]
Wambier, C.G.; Goren, A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J. Am. Acad. Dermatol., 2020, 83(1), 308-309.
[http://dx.doi.org/10.1016/j.jaad.2020.04.032] [PMID: 32283245]
[62]
Simmons, G.; Gosalia, D.N.; Rennekamp, A.J.; Reeves, J.D.; Diamond, S.L.; Bates, P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc. Natl. Acad. Sci. USA, 2005, 102(33), 11876-11881.
[http://dx.doi.org/10.1073/pnas.0505577102] [PMID: 16081529]
[63]
Gierer, S.; Bertram, S.; Kaup, F.; Wrensch, F.; Heurich, A.; Krämer-Kühl, A.; Welsch, K.; Winkler, M.; Meyer, B.; Drosten, C.; Dittmer, U.; von Hahn, T.; Simmons, G.; Hofmann, H.; Pöhlmann, S. The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. J. Virol., 2013, 87(10), 5502-5511.
[http://dx.doi.org/10.1128/JVI.00128-13] [PMID: 23468491]
[64]
Zhou, Y.; Vedantham, P.; Lu, K.; Agudelo, J.; Carrion, R., Jr; Nunneley, J.W.; Barnard, D.; Pöhlmann, S.; McKerrow, J.H.; Renslo, A.R.; Simmons, G. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res., 2015, 116, 76-84.
[http://dx.doi.org/10.1016/j.antiviral.2015.01.011] [PMID: 25666761]
[65]
Hammer, Q.; Rückert, T.; Romagnani, C. Natural killer cell specificity for viral infections. Nat. Immunol., 2018, 19(8), 800-808.
[http://dx.doi.org/10.1038/s41590-018-0163-6] [PMID: 30026479]
[66]
Zhou, L.; Huntington, K.; Zhang, S.; Carlsen, L.; So, E.Y.; Parker, C.; Sahin, I.; Safran, H.; Kamle, S.; Lee, C.M.; Lee, C.G.; Elias, J.A.; Campbell, K.S.; Naik, M.T.; Atwood, W.J.; Youssef, E.; Pachter, J.A.; Navaraj, A.; Seyhan, A.A.; Liang, O.; El-Deiry, W.S. Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells. bioRxiv, 2020, 2020.08.02.230839.
[PMID: 32793908]
[67]
Pushpakom, S.; Iorio, F.; Eyers, P.A.; Escott, K.J.; Hopper, S.; Wells, A.; Doig, A.; Guilliams, T.; Latimer, J.; McNamee, C.; Norris, A.; Sanseau, P.; Cavalla, D.; Pirmohamed, M. Drug repurposing: progress, challenges and recommendations. Nat. Rev. Drug Discov., 2019, 18(1), 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[68]
Chan, J.F.; Kok, K.H.; Zhu, Z.; Chu, H.; To, K.K.; Yuan, S.; Yuen, K.Y. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect., 2020, 9(1), 221-236.
[http://dx.doi.org/10.1080/22221751.2020.1719902] [PMID: 31987001]
[69]
Wu, G.; Zhao, T.; Kang, D.; Zhang, J.; Song, Y.; Namasivayam, V.; Kongsted, J.; Pannecouque, C.; De Clercq, E.; Poongavanam, V.; Liu, X.; Zhan, P. Overview of Recent Strategic Advances in Medicinal Chemistry. J. Med. Chem., 2019, 62(21), 9375-9414.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00359] [PMID: 31050421]
[70]
Zhang, S.; Zhang, J.; Gao, P.; Sun, L.; Song, Y.; Kang, D.; Liu, X.; Zhan, P. Efficient drug discovery by rational lead hybridization based on crystallographic overlay. Drug Discov. Today, 2019, 24(3), 805-813.
[http://dx.doi.org/10.1016/j.drudis.2018.11.021] [PMID: 30529326]
[71]
Fang, Z.; Song, Y.; Zhan, P.; Zhang, Q.; Liu, X. Conformational restriction: an effective tactic in ‘follow-on’-based drug discovery. Future Med. Chem., 2014, 6(8), 885-901.
[http://dx.doi.org/10.4155/fmc.14.50] [PMID: 24962281]
[72]
Bestle, D.; Heindl, M.R.; Limburg, H.; Van Lam Van, T.; Pilgram, O.; Moulton, H.; Stein, D.A.; Hardes, K.; Eickmann, M.; Dolnik, O.; Rohde, C.; Klenk, H.D.; Garten, W.; Steinmetzer, T.; Böttcher-Friebertshäuser, E. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance, 2020, 3(9), e202000786.
[http://dx.doi.org/10.26508/lsa.202000786] [PMID: 32703818]