Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

References

• http://www.emro.who.int/health-topics/mers-cov/mers-outbreaks.html.
   Google Scholar
• Omrani, A. S., J. A. Al-Tawfiq, and Z. A. Memish. 2015. Middle east respiratory syndrome coronavirus (MERS-CoV): animal to human interaction. Pathog. Glob. Health. 109:354–362. doi: 10.1080/20477724.2015.1122852.
   PubMed Web of Science ®Google Scholar
• Azhar, E. I., S. A. El-Kafrawy, S. A. Farraj, A. M. Hassan, M. S. Al-Saeed, A. M. Hashem, and T. A. Madani. 2014. Evidence for camel-to-human transmission of MERS coronavirus. N. Engl. J. Med. 370:2499–2505. doi: 10.1056/NEJMoa1401505.
   PubMed Web of Science ®Google Scholar
• Haagmans, B. L., S. H. Al Dhahiry, C. B. Reusken, V. S. Raj, M. Galiano, R. Myers, G. J. Godeke, M. Jonges, E. Farag, A. Diab, H. Ghobashy, F. Alhajri, M. Al-Thani, S. A. Al-Marri, H. E. Al Romaihi, A. Al Khal, A. Bermingham, A. D. Osterhaus, M. M. AlHajri, and M. P. Koopmans. 2014. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 14:140–145. doi: 10.1016/S1473-3099(13)70690-X.
   PubMed Web of Science ®Google Scholar
• Memish, Z. A., M. Cotten, B. Meyer, S. J. Watson, A. J. Alsahafi, A. A. Al Rabeeah, V. M. Corman, A. Sieberg, H. Q. Makhdoom, A. Assiri, M. Al Masri, S. Aldabbagh, B. J. Bosch, M. Beer, M. A. Muller, P. Kellam, and C. Drosten. 2014. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis 20:1012–1015. doi: 10.3201/eid2006.140402.
   Google Scholar
• Du, L., Y. Yang, Y. Zhou, L. Lu, F. Li, and S. Jiang. 2017. MERS-CoV spike protein: a key target for antivirals. Expert Opin. Ther. Targets. 21:131–143. doi: 10.1080/14728222.2017.1271415.
   PubMed Web of Science ®Google Scholar
• Walls, A. C., M. A. Tortorici, B. J. Bosch, B. Frenz, P. J. M. Rottier, F. DiMaio, F. A. Rey, and D. Veesler. 2016. Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer. Nature. 531:114–117. doi: 10.1038/nature16988.
   PubMed Web of Science ®Google Scholar
• Walls, A. C., M. A. Tortorici, B. Frenz, J. Snijder, W. Li, F. A. Rey, F. DiMaio, B. J. Bosch, and D. Veesler. 2016. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nat. Struct. Mol. Biol. 23:899–905. doi: 10.1038/nsmb.3293.
   PubMed Web of Science ®Google Scholar
• Xiong, X., M. A. Tortorici, J. Snijder, C. Yoshioka, A. C. Walls, W. Li, A. T. McGuire, F. A. Rey, B. J. Bosch, and D. Veesler. 2017. Glycan shield and fusion activation of a deltacoronavirus spike glycoprotein fine-tuned for enteric infections. J. Virol. doi: JVI.01628-17 [pii].
   Web of Science ®Google Scholar
• Kirchdoerfer, R. N., C. A. Cottrell, N. Wang, J. Pallesen, H. M. Yassine, H. L. Turner, K. S. Corbett, B. S. Graham, J. S. McLellan, and A. B. Ward. 2016. Pre-fusion structure of a human coronavirus spike protein. Nature. 531:118–121. doi: 10.1038/nature17200.
   PubMed Web of Science ®Google Scholar
• Shang, J., Y. Zheng, Y. Yang, C. Liu, Q. Geng, W. Tai, L. Du, Y. Zhou, W. Zhang, and F. Li. 2018. Cryo-Electron microscopy Structure of Porcine Deltacoronavirus spike protein in the prefusion state. J. Virol. 92. doi: 10.1128/JVI.01556-17. JVI.01556-17 [pii].
   Web of Science ®Google Scholar
• Shang, J., Y. Zheng, Y. Yang, C. Liu, Q. Geng, C. Luo, W. Zhang, and F. Li. 2018. Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins. PLoS Pathog. 14:e1007009. doi: 10.1371/journal.ppat.1007009.
   PubMed Web of Science ®Google Scholar
• Yuan, Y., D. Cao, Y. Zhang, J. Ma, J. Qi, Q. Wang, G. Lu, Y. Wu, J. Yan, Y. Shi, X. Zhang, and G. F. Gao. 2017. Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat. Commun. 8:15092. doi: 10.1038/ncomms15092.
   PubMed Web of Science ®Google Scholar
• Raj, V. S., H. Mou, S. L. Smits, D. H. Dekkers, M. A. Muller, R. Dijkman, D. Muth, J. A. Demmers, A. Zaki, R. A. Fouchier, V. Thiel, C. Drosten, P. J. Rottier, A. D. Osterhaus, B. J. Bosch, and B. L. Haagmans. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 495:251–254. doi: 10.1038/nature12005.
   PubMed Web of Science ®Google Scholar
• Mou, H., V. S. Raj, F. J. van Kuppeveld, P. J. Rottier, B. L. Haagmans, and B. J. Bosch. 2013. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J. Virol. 87:9379–9383. doi: 10.1128/JVI.01277-13.
   PubMed Web of Science ®Google Scholar
• Li, W., R. J. G. Hulswit, I. Widjaja, V. S. Raj, R. McBride, W. Peng, W. Widagdo, M. A. Tortorici, B. van Dieren, Y. Lang, J. W. M. van Lent, J. C. Paulson, C. A. M. de Haan, R. J. de Groot, F. J. M. van Kuppeveld, B. L. Haagmans, and B. J. Bosch. 2017. Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein. Proc. Natl. Acad. Sci. U. S. A. 114:E8508–E8517. doi: 10.1073/pnas.1712592114.
   PubMed Web of Science ®Google Scholar
• Corti, D., J. Zhao, M. Pedotti, L. Simonelli, S. Agnihothram, C. Fett, B. Fernandez-Rodriguez, M. Foglierini, G. Agatic, F. Vanzetta, R. Gopal, C. J. Langrish, N. A. Barrett, F. Sallusto, R. S. Baric, L. Varani, M. Zambon, S. Perlman, and A. Lanzavecchia. 2015. Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus. Proc. Natl. Acad. Sci. U. S. A. 112:10473–10478. doi: 10.1073/pnas.1510199112.
   PubMed Web of Science ®Google Scholar
• Du, L., G. Zhao, Y. Yang, H. Qiu, L. Wang, Z. Kou, X. Tao, H. Yu, S. Sun, C. T. Tseng, S. Jiang, F. Li, and Y. Zhou. 2014. A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein. J. Virol. 88:7045–7053. doi: 10.1128/JVI.00433-14.
   PubMed Web of Science ®Google Scholar
• Li, Y., Y. Wan, P. Liu, J. Zhao, G. Lu, J. Qi, Q. Wang, X. Lu, Y. Wu, W. Liu, B. Zhang, K. Y. Yuen, S. Perlman, G. F. Gao, and J. Yan. 2015. A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein. Cell Res. 25:1237–1249. doi: 10.1038/cr.2015.113.
   PubMed Web of Science ®Google Scholar
• Pascal, K. E., C. M. Coleman, A. O. Mujica, V. Kamat, A. Badithe, J. Fairhurst, C. Hunt, J. Strein, A. Berrebi, J. M. Sisk, K. L. Matthews, R. Babb, G. Chen, K. M. Lai, T. T. Huang, W. Olson, G. D. Yancopoulos, N. Stahl, M. B. Frieman, and C. A. Kyratsous. 2015. Pre- and postexposure efficacy of fully human antibodies against spike protein in a novel humanized mouse model of MERS-CoV infection. Proc. Natl. Acad. Sci. U. S. A. 112:8738–8743. doi: 10.1073/pnas.1510830112.
   PubMed Web of Science ®Google Scholar
• Jiang, L., N. Wang, T. Zuo, X. Shi, K. M. Poon, Y. Wu, F. Gao, D. Li, R. Wang, J. Guo, L. Fu, K. Y. Yuen, B. J. Zheng, X. Wang, and L. Zhang. 2014. Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci. Transl. Med. 6:234ra59. doi: 10.1126/scitranslmed.3008140.
   PubMed Web of Science ®Google Scholar
• Tang, X. C., S. S. Agnihothram, Y. Jiao, J. Stanhope, R. L. Graham, E. C. Peterson, Y. Avnir, A. S. Tallarico, J. Sheehan, Q. Zhu, R. S. Baric, and W. A. Marasco. 2014. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc. Natl. Acad. Sci. U. S. A. 111:E2018–E2026. doi: 10.1073/pnas.1402074111.
   PubMed Web of Science ®Google Scholar
• Ying, T., L. Du, T. W. Ju, P. Prabakaran, C. C. Lau, L. Lu, Q. Liu, L. Wang, Y. Feng, Y. Wang, B. J. Zheng, K. Y. Yuen, S. Jiang, and D. S. Dimitrov. 2014. Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J. Virol. 88:7796–7805. doi: 10.1128/JVI.00912-14.
   PubMed Web of Science ®Google Scholar
• Johnson, R. F., U. Bagci, L. Keith, X. Tang, D. J. Mollura, L. Zeitlin, J. Qin, L. Huzella, C. J. Bartos, N. Bohorova, O. Bohorov, C. Goodman, D. H. Kim, M. H. Paulty, J. Velasco, K. J. Whaley, J. C. Johnson, J. Pettitt, B. L. Ork, J. Solomon, N. Oberlander, Q. Zhu, J. Sun, M. R. Holbrook, G. G. Olinger, R. S. Baric, L. E. Hensley, P. B. Jahrling, and W. A. Marasco. 2016. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012. Virology. 490:49–58. doi: 10.1016/j.virol.2016.01.004.
   PubMed Web of Science ®Google Scholar
• Qiu, H., S. Sun, H. Xiao, J. Feng, Y. Guo, W. Tai, Y. Wang, L. Du, G. Zhao, and Y. Zhou. 2016. Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection. Antiviral Res. 132:141–148. doi: 10.1016/j.antiviral.2016.06.003.
   PubMed Web of Science ®Google Scholar
• Agrawal, A. S., T. Ying, X. Tao, T. Garron, A. Algaissi, Y. Wang, L. Wang, B. H. Peng, S. Jiang, D. S. Dimitrov, and C. T. Tseng. 2016. Passive transfer of A Germline-like neutralizing human monoclonal antibody Protects transgenic mice against lethal Middle East respiratory syndrome coronavirus infection. Sci. Rep. 6:31629. doi: 10.1038/srep31629.
   PubMed Web of Science ®Google Scholar
• Houser, K. V., L. Gretebeck, T. Ying, Y. Wang, L. Vogel, E. W. Lamirande, K. W. Bock, I. N. Moore, D. S. Dimitrov, and K. Subbarao. 2016. Prophylaxis With a Middle East respiratory syndrome coronavirus (MERS-CoV)-specific human monoclonal antibody Protects Rabbits from MERS-CoV infection. J. Infect. Dis. 213:1557–1561. doi: 10.1093/infdis/jiw080.
   PubMed Web of Science ®Google Scholar
• Yu, X., S. Zhang, L. Jiang, Y. Cui, D. Li, D. Wang, N. Wang, L. Fu, X. Shi, Z. Li, L. Zhang, and X. Wang. 2015. Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27. Sci. Rep. 5:13133. doi: 10.1038/srep13133.
   PubMed Web of Science ®Google Scholar
• Wang, L., W. Shi, M. G. Joyce, K. Modjarrad, Y. Zhang, K. Leung, C. R. Lees, T. Zhou, H. M. Yassine, M. Kanekiyo, Z. Y. Yang, X. Chen, M. M. Becker, M. Freeman, L. Vogel, J. C. Johnson, G. Olinger, J. P. Todd, U. Bagci, J. Solomon, D. J. Mollura, L. Hensley, P. Jahrling, M. R. Denison, S. S. Rao, K. Subbarao, P. D. Kwong, J. R. Mascola, W. P. Kong, and B. S. Graham. 2015. Evaluation of candidate vaccine approaches for MERS-CoV. Nat. Commun. 6:7712. doi: 10.1038/ncomms8712.
   PubMed Web of Science ®Google Scholar
• Wang, L., W. Shi, J. D. Chappell, M. G. Joyce, Y. Zhang, M. Kanekiyo, M. M. Becker, N. van Doremalen, R. Fischer, N. Wang, K. S. Corbett, M. Choe, R. D. Mason, J. G. Van Galen, T. Zhou, K. O. Saunders, K. M. Tatti, L. M. Haynes, P. D. Kwong, K. Modjarrad, W. P. Kong, J. S. McLellan, M. R. Denison, V. J. Munster, J. R. Mascola, and B. S. Graham. 2018. Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on MERS-CoV spike to avoid neutralization escape. J. Virol. doi: JVI.02002-17 [pii].
   Web of Science ®Google Scholar
• Qiu, X., G. Wong, J. Audet, A. Bello, L. Fernando, J. B. Alimonti, H. Fausther-Bovendo, H. Wei, J. Aviles, E. Hiatt, A. Johnson, J. Morton, K. Swope, O. Bohorov, N. Bohorova, C. Goodman, D. Kim, M. H. Pauly, J. Velasco, J. Pettitt, G. G. Olinger, K. Whaley, B. Xu, J. E. Strong, L. Zeitlin, and G. P. Kobinger. 2014. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 514:47–53. doi: 10.1038/nature13777.
   PubMed Web of Science ®Google Scholar
• Saphire, E. O., and M. J. Aman. 2016. Feverish Quest for Ebola Immunotherapy: Straight or Cocktail? Trends Microbiol. 24:684–686. doi: S0966-842X(16)30049-X [pii] doi: 10.1016/j.tim.2016.05.008
   PubMed Web of Science ®Google Scholar
• Saphire, E. O., S. L. Schendel, M. L. Fusco, K. Gangavarapu, B. M. Gunn, A. Z. Wec, P. J. Halfmann, J. M. Brannan, A. S. Herbert, X. Qiu, K. Wagh, S. He, E. E. Giorgi, J. Theiler, K. B. J. Pommert, T. B. Krause, H. L. Turner, C. D. Murin, J. Pallesen, E. Davidson, R. Ahmed, M. J. Aman, A. Bukreyev, D. R. Burton, J. E. Crowe Jr, C. W. Davis, G. Georgiou, F. Krammer, C. A. Kyratsous, J. R. Lai, C. Nykiforuk, M. H. Pauly, P. Rijal, A. Takada, A. R. Townsend, V. Volchkov, L. M. Walker, C. I. Wang, L. Zeitlin, B. J. Doranz, A. B. Ward, B. Korber, G. P. Kobinger, K. G. Andersen, Y. Kawaoka, G. Alter, K. Chandran, J. M. Dye, and Viral Hemorrhagic Fever Immunotherapeutic Consortium. 2018. Systematic analysis of monoclonal antibodies against Ebola virus GP defines Features that contribute to protection. Cell. 174:938–952. e13. doi: S0092-8674(18)30960-7 [pii] doi: 10.1016/j.cell.2018.07.033
   PubMed Web of Science ®Google Scholar
• Kyratsous, C., N. Stahl, and S. Sfvapalasingam. 2015. Regeneron Pharmaceuticals Inc. International publication number: WO2015179535.
   Google Scholar
• Walls, A. C., M. A. Tortorici, J. Snijder, X. Xiong, B. J. Bosch, F. A. Rey, and D. Veesler. 2017. Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc. Natl. Acad. Sci. U. S. A. 114:11157–11162. doi: 10.1073/pnas.1708727114.
   PubMed Web of Science ®Google Scholar
• Li, K., C. Wohlford-Lenane, S. Perlman, J. Zhao, A. K. Jewell, L. R. Reznikov, K. N. Gibson-Corley, D. K. Meyerholz, and P. B. McCray Jr. 2016. Middle East respiratory syndrome coronavirus causes multiple Organ Damage and lethal disease in mice transgenic for human Dipeptidyl Peptidase 4. J. Infect. Dis. 213:712–722. doi: 10.1093/infdis/jiv499.
   PubMed Web of Science ®Google Scholar
• World Health Organization. http://www.who.int/blueprint/what/research-development/meeting-report-prioritization.pdf?ua=1.
   Google Scholar
• Bossart, K. N., and C. C. Broder. 2006. Developments towards effective treatments for Nipah and Hendra virus infection. Expert Rev. Anti Infect. Ther. 4:43–55. doi: 10.1586/14787210.4.1.43.
   PubMedGoogle Scholar
• Lu, L. L., T. J. Suscovich, S. M. Fortune, and G. Alter. 2017. Beyond binding: antibody effector functions in infectious diseases. Nat. Rev. Immunol. 18:46–61. doi: 10.1038/nri.2017.106.
   PubMed Web of Science ®Google Scholar
• Overdijk, M. B., S. Verploegen, A. Ortiz Buijsse, T. Vink, J. H. Leusen, W. K. Bleeker, and P. W. Parren. 2012. Crosstalk between human IgG isotypes and murine effector cells. J. Immunol. 189:3430–3438. doi: jimmunol.1200356 [pii] doi: 10.4049/jimmunol.1200356
   PubMed Web of Science ®Google Scholar
• Audet, J., G. Wong, H. Wang, G. Lu, G. F. Gao, G. Kobinger, and X. Qiu. 2015. Molecular characterization of the monoclonal antibodies composing ZMAb: a protective cocktail against Ebola virus. Sci. Rep. 4:6881. doi: 10.1038/srep06881.
   Web of Science ®Google Scholar
• Qiu, X., J. Audet, G. Wong, S. Pillet, A. Bello, T. Cabral, J. E. Strong, F. Plummer, C. R. Corbett, J. B. Alimonti, and G. P. Kobinger. 2012. Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies. Sci. Transl. Med. 4:138ra81. doi: 10.1126/scitranslmed.3003876.
   PubMed Web of Science ®Google Scholar
• Pal, P., K. A. Dowd, J. D. Brien, M. A. Edeling, S. Gorlatov, S. Johnson, I. Lee, W. Akahata, G. J. Nabel, M. K. Richter, J. M. Smit, D. H. Fremont, T. C. Pierson, M. T. Heise, and M. S. Diamond. 2013. Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus. PLoS Pathog. 9:e1003312. doi: 10.1371/journal.ppat.1003312.
   PubMed Web of Science ®Google Scholar
• Bakker, A. B., W. E. Marissen, R. A. Kramer, A. B. Rice, W. C. Weldon, M. Niezgoda, C. A. Hanlon, S. Thijsse, H. H. Backus, J. de Kruif, B. Dietzschold, C. E. Rupprecht, and J. Goudsmit. 2005. Novel human monoclonal antibody combination effectively neutralizing natural rabies virus variants and individual in vitro escape mutants. J. Virol. 79:9062–9068. doi: 79/14/9062 [pii] doi: 10.1128/JVI.79.14.9062-9068.2005
   PubMed Web of Science ®Google Scholar
• Enjuanes, L., S. Zuniga, C. Castano-Rodriguez, J. Gutierrez-Alvarez, J. Canton, and I. Sola. 2016. Molecular Basis of coronavirus Virulence and vaccine development. Adv. Virus Res. 96:245–286. doi: S0065-3527(16)30042-2 [pii] doi: 10.1016/bs.aivir.2016.08.003
   PubMed Web of Science ®Google Scholar
• Corti, D., J. Voss, S. J. Gamblin, G. Codoni, A. Macagno, D. Jarrossay, S. G. Vachieri, D. Pinna, A. Minola, F. Vanzetta, C. Silacci, B. M. Fernandez-Rodriguez, G. Agatic, S. Bianchi, I. Giacchetto-Sasselli, L. Calder, F. Sallusto, P. Collins, L. F. Haire, N. Temperton, J. P. Langedijk, J. J. Skehel, and A. Lanzavecchia. 2011. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 333:850–856. doi: 10.1126/science.1205669
   PubMed Web of Science ®Google Scholar
• Furuyama, W., A. Marzi, A. Nanbo, E. Haddock, J. Maruyama, H. Miyamoto, M. Igarashi, R. Yoshida, O. Noyori, H. Feldmann, and A. Takada. 2016. Discovery of an antibody for pan-ebolavirus therapy. Sci. Rep. 6:20514. doi: 10.1038/srep20514.
   Google Scholar
• Gilchuk, P., N. Kuzmina, P. A. Ilinykh, K. Huang, B. M. Gunn, A. Bryan, E. Davidson, B. J. Doranz, H. L. Turner, M. L. Fusco, M. S. Bramble, N. A. Hoff, E. Binshtein, N. Kose, A. I. Flyak, R. Flinko, C. Orlandi, R. Carnahan, E. H. Parrish, A. M. Sevy, R. G. Bombardi, P. K. Singh, P. Mukadi, J. J. Muyembe-Tamfum, M. D. Ohi, E. O. Saphire, G. K. Lewis, G. Alter, A. B. Ward, A. W. Rimoin, A. Bukreyev, and J. E. Crowe Jr. 2018. Multifunctional Pan-ebolavirus antibody recognizes a site of broad Vulnerability on the ebolavirus glycoprotein. Immunity. . doi: S1074-7613(18)30300-5 [pii].
   PubMed Web of Science ®Google Scholar
• Kaname, Y., H. Tani, C. Kataoka, M. Shiokawa, S. Taguwa, T. Abe, K. Moriishi, T. Kinoshita, and Y. Matsuura. 2010. Acquisition of complement resistance through incorporation of CD55/decay-accelerating factor into viral particles bearing baculovirus GP64. J. Virol. 84:3210–3219. doi: 10.1128/JVI.02519-09.
   PubMed Web of Science ®Google Scholar
• Stalin Raj, V., N. M. A. Okba, J. Gutierrez-Alvarez, D. Drabek, B. van Dieren, W. Widagdo, M. M. Lamers, I. Widjaja, R. Fernandez-Delgado, I. Sola, A. Bensaid, M. P. Koopmans, J. Segales, A. D. M. E. Osterhaus, B. J. Bosch, L. Enjuanes, and B. L. Haagmans. 2018. Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection. Sci. Adv. 4:eaas9667. doi: 10.1126/sciadv.aas9667.
   PubMed Web of Science ®Google Scholar