(1) Watanabe, Y.; Bowden, T. A.; Wilson, I. A.; Crispin, M. Exploitation of Glycosylation in Enveloped Virus Pathobiology. Biochim. Biophys. Acta - Gen. Subj. 2019, 1863, 1480–1497.
(2) World Health Organization. Lassa Fever Research and Development Roadmap. 2018, No. May, 1–18.
(3) Ibukun, F. I. Inter-Lineage Variation of Lassa Virus Glycoprotein Epitopes: A Challenge to Lassa Virus Vaccine Development. Viruses 2020, 12, 386.
(4) Crispin, M.; Zeltina, A.; Zitzmann, N.; Bowden, T. A. Native Functionality and Therapeutic Targeting of Arenaviral Glycoproteins. Curr. Opin. Virol. 2016, 18, 70–75.
(5) Hastie, K. M.; Cross, R. W.; Harkins, S. S.; Zandonatti, M. A.; Koval, A. P.; Heinrich, M. L.; Rowland, M. M.; Robinson, J. E.; Geisbert, T. W.; Garry, R. F. et al. Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization. Cell 2019, 178, 1004-1015.e14.
(6) Hastie, K. M.; Igonet, S.; Sullivan, B. M.; Legrand, P.; Zandonatti, M. A.; Robinson, J. E.; Garry, R. F.; Rey, F. A.; Oldstone, M. B.; Saphire, E. O. Crystal Structure of the Prefusion Surface Glycoprotein of the Prototypic Arenavirus LCMV. Nat. Struct. Mol. Biol. 2016, 23, 513–521.
(7) Hastie, K. M.; Zandonatti, M. A.; Kleinfelter, L. M.; Heinrich, M. L.; Rowland, M. M.; Chandran, K.; Branco, L. M.; Robinson, J. E.; Garry, R. F.; Saphire, E. O. Structural Basis for Antibody-Mediated Neutralization of Lassa Virus. Science 2017, 356, 923–928.
(8) Li, S.; Sun, Z.; Pryce, R.; Parsy, M. L.; Fehling, S. K.; Schlie, K.; Siebert, C. A.; Garten, W.; Bowden, T. A.; Strecker, T. et al. Acidic PH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike. PLoS Pathog. 2016, 12, e1005418.
(9) Zeltina, A.; Bowden, T. A. Human Antibody Pieces Together the Puzzle of the Trimeric Lassa Virus Surface Antigen. Nat. Struct. Mol. Biol. 2017, 24, 559–560.
(10) Jae, L. T.; Raaben, M.; Herbert, A. S.; Kuehne, A. I.; Wirchnianski, A. S.; Soh, T. K.; Stubbs, S. H.; Janssen, H.; Damme, M.; Saftig, P. et al. Lassa Virus Entry Requires a Trigger-Induced Receptor Switch. Science 2014, 344, 1506–1510.
(11) Torriani, G.; Galan-Navarro, C.; Kunz, S. Lassa Virus Cell Entry Reveals New Aspects of Virus-Host Cell Interaction. J. Virol. 2017, 91, 1–8.
(12) Watanabe, Y.; Raghwani, J.; Allen, J. D.; Seabright, G. E.; Li, S.; Moser, F.; Huiskonen, J. T.; Strecker, T.; Bowden, T. A.; Crispin, M. Structure of the Lassa Virus Glycan Shield Provides a Model for Immunological Resistance. Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 7320–7325.
(13) Robinson, J. E.; Hastie, K. M.; Cross, R. W.; Yenni, R. E.; Elliott, D. H.; Rouelle, J. A.; Kannadka, C. B.; Smira, A. A.; Garry, C. E.; Bradley, B. T. et al. Most Neutralizing Human Monoclonal Antibodies Target Novel Epitopes Requiring Both Lassa Virus Glycoprotein Subunits. Nat. Commun. 2016, 7, 11544.
(14) Sommerstein, R.; Flatz, L.; Remy, M. M.; Malinge, P.; Magistrelli, G.; Fischer, N.; Sahin, M.; Bergthaler, A.; Igonet, S.; ter Meulen, J. et al. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection. PLoS Pathog. 2015, 11, e1005276.
(15) Sikora, M.; von Bülow, S.; Blanc, F. E. C.; Gecht, M.; Covino, R.; Hummer, G. Map of SARS-CoV-2 Spike Epitopes Not Shielded by Glycans. bioRxiv 2020.
(16) Casalino, L.; Gaieb, Z.; Goldsmith, J. A.; Hjorth, C. K.; Dommer, A. C.; Harbison, A. M.; Fogarty, C. A.; Barros, E. P.; Taylor, B. C.; Mclellan, J. S. et al. Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein. ACS Cent. Sci. 2020, 6, 1722–1734.
(17) Grant, O. C.; Montgomery, D.; Ito, K.; Woods, R. J. Analysis of the SARS-CoV-2 Spike Protein Glycan Shield Reveals Implications for Immune Recognition. Sci. Rep. 2020, 10, 1– 18.
(18) Watanabe, Y.; Berndsen, Z. T.; Raghwani, J.; Seabright, G. E.; Allen, J. D.; Pybus, O. G.; McLellan, J. S.; Wilson, I. A.; Bowden, T. A.; Ward, A. B. et al. Vulnerabilities in Coronavirus Glycan Shields despite Extensive Glycosylation. Nat. Commun. 2020, 11, 2688.
(19) Pritchard, L. K.; Spencer, D. I. R.; Royle, L.; Bonomelli, C.; Seabright, G. E.; Behrens, A. J.; Kulp, D. W.; Menis, S.; Krumm, S. A.; Dunlop, D. C. et al. Glycan Clustering Stabilizes the Mannose Patch of HIV-1 and Preserves Vulnerability to Broadly Neutralizing Antibodies. Nat. Commun. 2015, 6, 1–11.
(20) Behrens, A. J.; Vasiljevic, S.; Pritchard, L. K.; Harvey, D. J.; Andev, R. S.; Krumm, S. A.; Struwe, W. B.; Cupo, A.; Kumar, A.; Zitzmann, N. et al. Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep. 2016, 14, 2695–2706.
(21) Coss, K. P.; Vasiljevic, S.; Pritchard, L. K.; Krumm, S. A.; Glaze, M.; Madzorera, S.; Moore, P. L.; Crispin, M.; Doores, K. J. HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual. J. Virol. 2016, 90, 11132–11144.
(22) Seabright, G. E.; Cottrell, C. A.; van Gils, M. J.; D’addabbo, A.; Harvey, D. J.; Behrens, A. J.; Allen, J. D.; Watanabe, Y.; Maker, A.; Vasiljevic, S. et al. Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions. bioRxiv 2020, 2020.02.21.959981.
(23) Crispin, M.; Ward, A. B.; Wilson, I. A. Structure and Immune Recognition of the HIV Glycan Shield. Annu. Rev. Biophys. 2018, 47, 499–523.
(24) Baral, P.; Pavadai, E.; Gerstman, B. S.; Chapagain, P. P. In-Silico Identification of the Vaccine Candidate Epitopes against the Lassa Virus Hemorrhagic Fever. Sci. Rep. 2020, 10, 7667.
(25) Verma, S. K.; Yadav, S.; Kumar, A. In Silico Prediction of B- and T- Cell Epitope on Lassa Virus Proteins for Peptide Based Subunit Vaccine Design. Adv. Biomed. Res. 2015, 4, 201– 201.
(26) Park, S. J.; Lee, J.; Qi, Y.; Kern, N. R.; Lee, H. S.; Jo, S.; Joung, I.; Joo, K.; Lee, J.; Im, W. CHARMM-GUI Glycan Modeler for Modeling and Simulation of Carbohydrates and Glycoconjugates. Glycobiology 2019, 29, 320–331.
(27) Ko, J.; Park, H.; Seok, C. GalaxyTBM: Template-Based Modeling by Building a Reliable Core and Refining Unreliable Local Regions. BMC Bioinformatics 2012, 13, 198.
(28) Olsson, M. H. M.; SØndergaard, C. R.; Rostkowski, M.; Jensen, J. H. PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical p K a Predictions. J. Chem. Theory Comput. 2011, 7, 525–537.
(29) Kobayashi, C.; Jung, J.; Matsunaga, Y.; Mori, T.; Ando, T.; Tamura, K.; Kamiya, M.; Sugita, Y. GENESIS 1.1: A Hybrid-Parallel Molecular Dynamics Simulator with Enhanced Sampling Algorithms on Multiple Computational Platforms. J. Comput. Chem. 2017, 38, 2193–2206.
(30) Jung, J.; Mori, T.; Kobayashi, C.; Matsunaga, Y.; Yoda, T.; Feig, M.; Sugita, Y. GENESIS: A Hybrid-Parallel and Multi-Scale Molecular Dynamics Simulator with Enhanced Sampling Algorithms for Biomolecular and Cellular Simulations. Wiley Interdiscip. Rev. Comput. Mol. Sci. 2015, 5, 310–323.
(31) Huang, J.; Rauscher, S.; Nawrocki, G.; Ran, T.; Feig, M.; De Groot, B. L.; Grubmüller, H.; MacKerell, A. D. CHARMM36m: An Improved Force Field for Folded and Intrinsically Disordered Proteins. Nat. Methods 2016, 14, 71–73.
(32) Best, R. B.; Zhu, X.; Shim, J.; Lopes, P. E. M.; Mittal, J.; Feig, M.; MacKerell, A. D. Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone φ, ψ and Side-Chain Χ1 and Χ2 Dihedral Angles. J. Chem. Theory Comput. 2012, 8, 3257–3273.
(33) Guvench, O.; Greenr, S. N.; Kamath, G.; Brady, J. W.; Venable, R. M.; Pastor, R. W.; Mackerell, A. D. Additive Empirical Force Field for Hexopyranose Monosaccharides. J. Comput. Chem. 2008, 29, 2543–2564.
(34) Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of Simple Potential Functions for Simulating Liquid Water. J. Chem. Phys. 1983, 79, 926– 935.
(35) Ryckaert, J. P.; Ciccotti, G.; Berendsen, H. J. C. Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes. J. Comput. Phys. 1977, 23, 327–341.
(36) Miyamoto, S.; Kollman, P. A. Settle: An Analytical Version of the SHAKE and RATTLE Algorithm for Rigid Water Models. J. Comput. Chem. 1992, 13, 952–962.
(37) Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. A Smooth Particle Mesh Ewald Method. J. Chem. Phys. 1995, 103, 8577–8593.
(38) Darden, T.; York, D.; Pedersen, L. Particle Mesh Ewald: An N·log(N) Method for Ewald Sums in Large Systems. J. Chem. Phys. 1993, 98, 10089–10092.
(39) Steinbach, P. J.; Brooks, B. R. New Spherical‐cutoff Methods for Long‐range Forces in Macromolecular Simulation. J. Comput. Chem. 1994, 15, 667–683.
(40) Tuckerman, M.; Berne, B. J.; Martyna, G. J. Reversible Multiple Time Scale Molecular Dynamics. J. Chem. Phys. 1992, 97, 1990–2001.
(41) Bussi, G.; Donadio, D.; Parrinello, M. Canonical Sampling through Velocity Rescaling. J. Chem. Phys. 2007, 126, 014101.
(42) Bussi, G.; Zykova-Timan, T.; Parrinello, M. Isothermal-Isobaric Molecular Dynamics Using Stochastic Velocity Rescaling. J. Chem. Phys. 2009, 130, 074101.
(43) Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual Molecular Dynamics. J. Mol. Graph. 1996, 14, 33–38.
(44) Shrake, A.; Rupley, J. A. Environment and Exposure to Solvent of Protein Atoms. Lysozyme and Insulin. J. Mol. Biol. 1973, 79, 351–371.
(45) Delano, W. L. The PyMOL Molecular Graphics System. 2002.
(46) Jespersen, M. C.; Peters, B.; Nielsen, M.; Marcatili, P. BepiPred-2.0: Improving SequenceBased B-Cell Epitope Prediction Using Conformational Epitopes. Nucleic Acids Res. 2017, 45, W24–W29.
(47) Ponomarenko, J.; Bui, H. H.; Li, W.; Fusseder, N.; Bourne, P. E.; Sette, A.; Peters, B. ElliPro: A New Structure-Based Tool for the Prediction of Antibody Epitopes. BMC Bioinformatics 2008, 9, 514.
(48) Doores, K. J.; Bonomelli, C.; Harvey, D. J.; Vasiljevic, S.; Dwek, R. A.; Burton, D. R.; Crispin, M.; Scanlan, C. N. Envelope Glycans of Immunodeficiency Virions Are Almost Entirely Oligomannose Antigens. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 13800–13805.
(49) Acciani, M.; Alston, J. T.; Zhao, G.; Reynolds, H.; Ali, A. M.; Xu, B.; Brindley, M. A. Mutational Analysis of Lassa Virus Glycoprotein Highlights Regions Required for AlphaDystroglycan Utilization. J. Virol. 2017, 91.
(50) Zhu, X.; Liu, Y.; Guo, J.; Wang, Z.; Cao, J.; Xiao, G.; Wang, W. Effects of N-Linked Glycan of Lassa Virus Envelope Glycoprotein on the Immune Response. bioRxiv 2020, 2020.09.29.319855.
(51) Wei, X.; Decker, J. M.; Wang, S.; Hui, H.; Kappes, J. C.; Wu, X.; Salazar-Gonzalez, J. F.; Salazar, M. G.; Kilby, J. M.; Saag, M. S. et al. Antibody Neutralization and Escape by HIV1. Nature 2003, 422, 307–312.
(52) Berndsen, Z. T.; Chakraborty, S.; Wang, X.; Cottrell, C. A.; Torres, J. L.; Diedrich, J. K.; López, C. A.; Yates, J. R.; van Gils, M. J.; Paulson, J. C. et al. Visualization of the HIV-1 Env Glycan Shield across Scales. Proc. Natl. Acad. Sci. U. S. A. 2020, 117, 28014–28025.
(53) Yang, M.; Huang, J.; Simon, R.; Wang, L. X.; MacKerell, A. D. Conformational Heterogeneity of the HIV Envelope Glycan Shield. Sci. Rep. 2017, 7, 4435.
(54) Falkowska, E.; Le, K. M.; Ramos, A.; Doores, K. J.; Lee, J. H.; Blattner, C.; Ramirez, A.; Derking, R.; vanGils, M. J.; Liang, C. H. et al. Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of Gp41 on Cleaved Envelope Trimers. Immunity 2014, 40, 657–668.
(55) Blattner, C.; Lee, J. H.; Sliepen, K.; Derking, R.; Falkowska, E.; delaPeña, A. T.; Cupo, A.; Julien, J. P.; vanGils, M.; Lee, P. S. et al. Structural Delineation of a Quaternary, CleavageDependent Epitope at the Gp41-Gp120 Interface on Intact HIV-1 Env Trimers. Immunity 2014, 40, 669–680.
(56) Dowling, W.; Thompson, E.; Badger, C.; Mellquist, J. L.; Garrison, A. R.; Smith, J. M.; Paragas, J.; Hogan, R. J.; Schmaljohn, C. Influences of Glycosylation on Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines. J. Virol. 2007, 81, 1821–1837.
(57) Sugita, Y.; Okamoto, Y. Replica-Exchange Molecular Dynamics Method for Protein Folding. Chem. Phys. Lett. 1999, 314, 141–151.
(58) Nishima, W.; Miyashita, N.; Yamaguchi, Y.; Sugita, Y.; Re, S. Effect of Bisecting GlcNAc and Core Fucosylation on Conformational Properties of Biantennary Complex-Type NGlycans in Solution. J. Phys. Chem. B 2012, 116, 8504–8512.
(59) Re, S.; Nishima, W.; Miyashita, N.; Sugita, Y. Conformational Flexibility of N-Glycans in Solution Studied by REMD Simulations. Biophys. Rev. 2012, 4, 179–187.
(60) Galvelis, R.; Re, S.; Sugita, Y. Enhanced Conformational Sampling of N-Glycans in Solution with Replica State Exchange Metadynamics. J. Chem. Theory Comput. 2017, 13, 1934–1942.
(61) Galvelis, R.; Sugita, Y. Replica State Exchange Metadynamics for Improving the Convergence of Free Energy Estimates. J. Comput. Chem. 2015, 36, 1446–1455.
(62) Kamiya, M.; Sugita, Y. Flexible Selection of the Solute Region in Replica Exchange with Solute Tempering: Application to Protein-Folding Simulations. J. Chem. Phys. 2018, 149, 072304.
(63) Liu, P.; Kim, B.; Friesner, R. A.; Berne, B. J. Replica Exchange with Solute Tempering: A Method for Sampling Biological Systems in Explicit Water. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 13749–13754.
(64) Wang, L.; Friesner, R. A.; Berne, B. J. Replica Exchange with Solute Scaling: A More Efficient Version of Replica Exchange with Solute Tempering (REST2). J. Phys. Chem. B 2011, 115, 9431–9438.
(65) Terakawa, T.; Kameda, T.; Takada, S. On Easy Implementation of a Variant of the Replica Exchange with Solute Tempering in GROMACS. J. Comput. Chem. 2011, 32, 1228–1234.
(66) Miao, Y.; Sinko, W.; Pierce, L.; Bucher, D.; Walker, R. C.; McCammon, J. A. Improved Reweighting of Accelerated Molecular Dynamics Simulations for Free Energy Calculation. J. Chem. Theory Comput. 2014, 10, 2677–2689.
(67) Sugita, Y.; Kamiya, M.; Oshima, H.; Re, S. Replica-Exchange Methods for Biomolecular Simulations. Methods Mol. Biol. 2019, 2022, 155–177.
(68) Raoufi, E.; Hemmati, M.; Eftekhari, S.; Khaksaran, K.; Mahmodi, Z.; Farajollahi, M. M.; Mohsenzadegan, M. Epitope Prediction by Novel Immunoinformatics Approach: A State-ofthe-Art Review. Int. J. Pept. Res. Ther. 2020, 26, 1155–1163.