[en] The SARS-CoV-2 pandemic spurred numerous research endeavors to comprehend the virus and mitigate its global severity. Understanding the binding interface between the virus and human receptors is pivotal to these efforts and paramount to curbing infection and transmission. Here we employ atomic force microscopy and steered molecular dynamics simulation to explore SARS-CoV-2 receptor binding domain (RBD) variants and angiotensin-converting enzyme 2 (ACE2), examining the impact of mutations at key residues upon binding affinity. Our results show that the Omicron and Delta variants possess strengthened binding affinity in comparison to the Mu variant. Further, using sera from individuals either vaccinated or with acquired immunity following Delta strain infection, we assess the impact of immunity upon variant RBD/ACE2 complex formation. Single-molecule force spectroscopy analysis suggests that vaccination before infection may provide stronger protection across variants. These results underscore the need to monitor antigenic changes in order to continue developing innovative and effective SARS-CoV-2 abrogation strategies.
Disciplines :
Immunology & infectious disease
Author, co-author :
Ray, Ankita ; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Minh Tran, Thu Thi ; Faculty of Materials Science and Technology, University of Science-VNU HCM, 227 Nguyen Van Cu Street, District 5, 700000 Ho Chi Minh City, Vietnam ; Vietnam National University, 700000 Ho Chi Minh City, Vietnam
Santos Natividade, Rita Dos ; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Moreira, Rodrigo A; Basque Center for Applied Mathematics, Mazarredo 14, 48009 Bilbao, Spain
Simpson, Joshua D ; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Mohammed, Danahe; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Koehler, Melanie; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
L Petitjean, Simon J; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Zhang, Qingrong; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Gillet, Laurent ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Poma, Adolfo B ; Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106 Warsaw, Poland
Alsteens, David ; Louvain Institute of Biomolecular Science and Technology, Université catholique de Louvain, 1348 Louvain-la-Neuve, Belgium ; WELBIO department, WEL Research Institute, 1300 Wavre, Belgium
NCN - Narodowe Centrum Nauki UCL - Université Catholique de Louvain Fondation Louvain HCMUS - Ho Chi Minh City University of Science F.R.S.-FNRS - Fonds de la Recherche Scientifique EU - European Union
Funding text :
This work was supported by the Université catholique de Louvain, the Foundation Louvain, and the Fonds National de la Recherche Scientifique (F.R.S.-FNRS) under the Excellence of Science (EOS) program (grant ID 40007527). This project received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 758224), from the FNRS-Welbio (Grant # CR-2019S-01). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the paper. A.R. is an FSR incoming postdoctoral fellow of Université catholique de Louvain. J.D.S. and D.A. are postdoctoral researcher and senior research associate at the F.R.S.-FNRS. A.B.P. acknowledges financial support from the National Science Center, Poland, under grant 2022/45/B/NZ1/02519 and Polish high-performance computing infrastructure PLGrid (HPC Centers: ACK Cyfronet AGH) for providing computer facilities and support within computational grant no. PLG/2023/016519. T.T.M.T. acknowledges financial support by Vietnam National University, Ho Chi Minh City (VNU-HCM) under grant number C2020-18-19. Cartoons in b and a were created with BioRender.com .
Harvey, W. T.; Carabelli, A. M.; Jackson, B.; Gupta, R. K.; Thomson, E. C.; Harrison, E. M.; Ludden, C.; Reeve, R.; Rambaut, A.; Peacock, S. J.; Robertson, D. L. SARS-CoV-2 Variants, Spike Mutations and Immune Escape. Nat. Rev. Microbiol. 2021, 19 ( 7), 409- 424, 10.1038/s41579-021-00573-0
Tao, K.; Tzou, P. L.; Nouhin, J.; Gupta, R. K.; de Oliveira, T.; Kosakovsky Pond, S. L.; Fera, D.; Shafer, R. W. The Biological and Clinical Significance of Emerging SARS-CoV-2 Variants. Nat. Rev. Genet. 2021, 22 ( 12), 757- 773, 10.1038/s41576-021-00408-x
Mccallum, M.; Czudnochowski, N.; Rosen, L. E.; Zepeda, S. K.; Bowen, J. E.; Walls, A. C.; Hauser, K.; Joshi, A.; Stewart, C.; Dillen, J. R.; Powell, A. E.; Croll, T. I.; Nix, J.; Virgin, H. W.; Corti, D. Evasion and Receptor Engagement. Science (80-.). 2022, 375 ( 6583), 864- 868, 10.1126/science.abn8652
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, 667 ( 6485), 1444, 10.1126/science.abb2762
Zhu, X.; Mannar, D.; Srivastava, S. S..; Berezuk, A. M..; Demers, J.-P.; Saville, J. W.; Leopold, K.; Li, W.; Dimitrov, S.; Tuttle, K. S.; Zhou, S.; Chittori, S.; Subramaniam, S. Cryo-Electron Microscopy Structures of the N501Y SARS-CoV-2 Spike Protein in Complex with ACE2 and 2 Potent Neutralizing Antibodies. PLoS Biol. 2021, 2, e3001237, 10.1371/journal.pbio.3001237
Bai, C.; Wang, J.; Chen, G.; Zhang, H.; An, K.; Xu, P.; Du, Y.; Ye, R. D.; Saha, A.; Zhang, A.; Warshel, A. Predicting Mutational Effects on Receptor Binding of the Spike Protein of SARS-CoV-2 Variants. J. Am. Chem. Soc. 2021, 143 ( 42), 17646- 17654, 10.1021/jacs.1c07965
Xiong, X.; Qu, K.; Ciazynska, K. A.; Hosmillo, M.; Carter, A. P.; Ebrahimi, S.; Ke, Z.; Scheres, S. H. W.; Bergamaschi, L.; Grice, G. L.; Zhang, Y.; Bradley, J.; Lyons, P. A.; Smith, K. G. C.; Toshner, M.; Elmer, A.; Ribeiro, C.; Kourampa, J.; Jose, S.; Kennet, J.; Rowlands, J.; Meadows, A.; O’Brien, C.; Rastall, R.; Crucusio, C.; Hewitt, S.; Price, J.; Calder, J.; Canna, L.; Bucke, A.; Tordesillas, H.; Harris, J.; Ruffolo, V.; Domingo, J.; Graves, B.; Butcher, H.; Caputo, D.; Le Gresley, E.; Dunmore, B. J.; Martin, J.; Legchenko, E.; Treacy, C.; Huang, C.; Wood, J.; Sutcliffe, R.; Hodgson, J.; Shih, J.; Graf, S.; Tong, Z.; Mescia, F.; Tilly, T.; O’Donnell, C.; Hunter, K.; Pointon, L.; Pond, N.; Wylot, M.; Jones, E.; Fawke, S.; Bullman, B.; Bergamaschi, L.; Turner, L.; Jarvis, I.; Omarjee, O.; De Sa, A.; Marsden, J.; Betancourt, A.; Perera, M.; Epping, M.; Richoz, N.; Bower, G.; Sharma, R.; Nice, F.; Huhn, O.; Stark, H.; Walker, N.; Stirrups, K.; Ovington, N.; Dewhust, E.; Li, E.; Papadia, S.; Nathan, J. A.; Baker, S.; James, L. C.; Baxendale, H. E.; Goodfellow, I.; Doffinger, R.; Briggs, J. A. G. A Thermostable, Closed SARS-CoV-2 Spike Protein Trimer. Nat. Struct. Mol. Biol. 2020, 27 ( 10), 934- 941, 10.1038/s41594-020-0478-5
Korber, B.; Fischer, W. M.; Gnanakaran, S.; Yoon, H.; Theiler, J.; Abfalterer, W.; Hengartner, N.; Giorgi, E. E.; Bhattacharya, T.; Foley, B.; Hastie, K. M.; Parker, M. D.; Partridge, D. G.; Evans, C. M.; Freeman, T. M.; de Silva, T. I.; Angyal, A.; Brown, R. L.; Carrilero, L.; Green, L. R.; Groves, D. C.; Johnson, K. J.; Keeley, A. J.; Lindsey, B. B.; Parsons, P. J.; Raza, M.; Rowland-Jones, S.; Smith, N.; Tucker, R. M.; Wang, D.; Wyles, M. D.; McDanal, C.; Perez, L. G.; Tang, H.; Moon-Walker, A.; Whelan, S. P.; LaBranche, C. C.; Saphire, E. O.; Montefiori, D. C. Tracking Changes in SARS-CoV-2 Spike: Evidence That D614G Increases Infectivity of the COVID-19 Virus. Cell 2020, 182 ( 4), 812- 827, 10.1016/j.cell.2020.06.043
Mansbach, R. A.; Chakraborty, S.; Nguyen, K.; Montefiori, D. C.; Korber, B.; Gnanakaran, S. The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State. Sci. Adv. 2021, 7 ( 16), 1- 10, 10.1126/sciadv.abf3671
Gobeil, S. M. C.; Janowska, K.; McDowell, S.; Mansouri, K.; Parks, R.; Manne, K.; Stalls, V.; Kopp, M. F.; Henderson, R.; Edwards, R. J.; Haynes, B. F.; Acharya, P. D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction. Cell Rep. 2021, 34 ( 2), 108630, 10.1016/j.celrep.2020.108630
Du, W.; Hurdiss, D. L.; Drabek, D.; Mykytyn, A. Z.; Kaiser, F. K.; González-Hernández, M.; Muñoz-Santos, D.; Lamers, M. M.; van Haperen, R.; Li, W.; Drulyte, I.; Wang, C.; Sola, I.; Armando, F.; Beythien, G.; Ciurkiewicz, M.; Baumgärtner, W.; Guilfoyle, K.; Smits, T.; van der Lee, J.; van Kuppeveld, F. J. M.; van Amerongen, G.; Haagmans, B. L.; Enjuanes, L.; Osterhaus, A. D. M. E.; Grosveld, F.; Bosch, B. J. An ACE2-Blocking Antibody Confers Broad Neutralization and Protection against Omicron and Other SARS-CoV-2 Variants of Concern. Sci. Immunol. 2022, 7 ( 73), eabp9312 10.1126/sciimmunol.abp9312
Wang, P.; Nair, M. S.; Liu, L.; Iketani, S.; Luo, Y.; Guo, Y.; Wang, M.; Yu, J.; Zhang, B.; Kwong, P. D.; Graham, B. S.; Mascola, J. R.; Chang, J. Y.; Yin, M. T.; Sobieszczyk, M.; Kyratsous, C. A.; Shapiro, L.; Sheng, Z.; Huang, Y.; Ho, D. D. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. Nature 2021, 593 ( May), 130, 10.1038/s41586-021-03398-2
Simpson, J. D.; Ray, A.; Marcon, C.; Dos Santos Natividade, R.; Dorrazehi, G. M.; Durlet, K.; Koehler, M.; Alsteens, D. Single-Molecule Analysis of SARS-CoV-2 Binding to C-Type Lectin Receptors. Nano Lett. 2023, 23, 1496, 10.1021/acs.nanolett.2c04931
McCallum, M.; De Marco, A.; Lempp, F. A.; Tortorici, M. A.; Pinto, D.; Walls, A. C.; Beltramello, M.; Chen, A.; Liu, Z.; Zatta, F.; Zepeda, S.; di Iulio, J.; Bowen, J. E.; Montiel-Ruiz, M.; Zhou, J.; Rosen, L. E.; Bianchi, S.; Guarino, B.; Fregni, C. S.; Abdelnabi, R.; Foo, S. Y. C.; Rothlauf, P. W.; Bloyet, L. M.; Benigni, F.; Cameroni, E.; Neyts, J.; Riva, A.; Snell, G.; Telenti, A.; Whelan, S. P. J.; Virgin, H. W.; Corti, D.; Pizzuto, M. S.; Veesler, D. N-Terminal Domain Antigenic Mapping Reveals a Site of Vulnerability for SARS-CoV-2. Cell 2021, 184 ( 9), 2332- 2347, 10.1016/j.cell.2021.03.028
Xie, Y.; Butler, M. Quantitative Profiling of N-Glycosylation of SARS-CoV-2 Spike Protein Variants. Glycobiology 2023, 33 ( 3), 188- 202, 10.1093/glycob/cwad007
Bauer, M. S.; Gruber, S.; Hausch, A.; Melo, M. C. R.; Gomes, P. S. F. C.; Nicolaus, T.; Milles, L. F.; Gaub, H. E.; Bernardi, R. C.; Lipfert, J. Single-Molecule Force Stability of the SARS-CoV-2-ACE2 Interface in Variants-of-Concern. Nat. Nanotechnol. 2023, 10.1038/s41565-023-01536-7
Yang, J.; Petitjean, S. J. L.; Koehler, M.; Zhang, Q.; Dumitru, A. C.; Chen, W.; Derclaye, S.; Vincent, S. P.; Soumillion, P.; Alsteens, D. Molecular Interaction and Inhibition of SARS-CoV-2 Binding to the ACE2 Receptor. Nat. Commun. 2020, 11 ( 1), 4541, 10.1038/s41467-020-18319-6
Miotto, M.; Di Rienzo, L.; Gosti, G.; Bo’, L.; Parisi, G.; Piacentini, R.; Boffi, A.; Ruocco, G.; Milanetti, E. Inferring the Stabilization Effects of SARS-CoV-2 Variants on the Binding with ACE2 Receptor. Commun. Biol. 2022, 5 ( 1), 1- 13, 10.1038/s42003-021-02946-w
Cox, M. G.; Peacock, T. P.; Harvey, W. T.; Hughes, J.; Wright, D. W.; Willett, B. J.; Thomson, E.; Gupta, R. K.; Peacock, S. J.; Robertson, D. L.; Carabelli, A. M. SARS-CoV-2 Variant Evasion of Monoclonal Antibodies Based on in Vitro Studies. Nat. Rev. Microbiol. 2023, 21 ( 2), 112- 124, 10.1038/s41579-022-00809-7
Binning, G.; Quate, C. F.; Gerber, C. Atomic Force Microscope. Phys. Rev. Lett. 1986, 56 ( 9), 930, 10.1103/PhysRevLett.56.930
Viljoen, A.; Mathelié-Guinlet, M.; Ray, A.; Strohmeyer, N.; Oh, Y. J.; Hinterdorfer, P.; Müller, D. J.; Alsteens, D.; Dufrêne, Y. F. Force Spectroscopy of Single Cells Using Atomic Force Microscopy. Nat. Rev. Methods Prim. 2021, 1, 63, 10.1038/s43586-021-00062-x
Koehler, M.; Ray, A.; Moreira, R. A.; Juniku, B.; Poma, A. B.; Alsteens, D. Molecular Insights into Receptor Binding Energetics and Neutralization of SARS-CoV-2 Variants. Nat. Commun. 2021, 12 ( 1), 1- 13, 10.1038/s41467-021-27325-1
Bauer, M. S.; Gruber, S.; Hausch, A.; Gomes, P. S. F. C.; Milles, L. F.; Nicolaus, T.; Schendel, L. C.; Navajas, P.; Procko, E.; Lietha, D.; Melo, M. C. R.; Bernardi, R. C.; Gaub, H. E.; Lipfert, J. A Tethered Ligand Assay to Probe SARS-CoV-2:ACE2 Interactions. Proc. Natl. Acad. Sci. U. S. A. 2022, 119 ( 14), 1- 11, 10.1073/pnas.2114397119
Shajahan, A.; Pepi, L. E.; Kumar, B.; Murray, N. B.; Azadi, P. Site Specific N- and O-Glycosylation Mapping of the Spike Proteins of SARS-CoV-2 Variants of Concern. Sci. Rep. 2023, 13 ( 1), 10053, 10.1038/s41598-023-33088-0
Cai, Y.; Zhang, J.; Xiao, T.; Peng, H.; Sterling, S. M.; Walsh, R. M.; Rawson, S.; Rits-Volloch, S.; Chen, B. Distinct Conformational States of SARS-CoV-2 Spike Protein. Science (80-.). 2020, 369 ( 6511), 1586- 1592, 10.1126/science.abd4251
Hane, F. T.; Attwood, S. J.; Leonenko, Z. Comparison of Three Competing Dynamic Force Spectroscopy Models to Study Binding Forces of Amyloid-β (1-42). Soft Matter 2014, 10 ( 12), 1924- 1930, 10.1039/c3sm52257a
Evans, E.; Ritchie, K. Dynamic Strength of Molecular Adhesion Bonds. Biophys. J. 1997, 72 ( 4), 1541- 1555, 10.1016/S0006-3495(97)78802-7
Evans, E. Energy Landscapes of Biomolecular Adhesion and Receptor Anchoring at Interfaces Explored with Dynamic Force Spectroscopy. Faraday Discuss. 1998, 1- 16, 10.1039/a809884k
Rankl, C.; Kienberger, F.; Wildling, L.; Wruss, J.; Gruber, H. J.; Blaas, D.; Hinterdorfer, P. Multiple Receptors Involved in Human Rhinovirus Attachment to Live Cells. Proc. Natl. Acad. Sci. U. S. A. 2008, 105 ( 46), 17778- 17783, 10.1073/pnas.0806451105
Delguste, M.; Koehler, M.; Gillet, L.; Alsteens, D. Topography Imaging of Herpesvirus in Native Condition Using Atomic Force Microscopy. Clin. Microbiol. Infect. 2018, 24 ( 6), 610- 611, 10.1016/j.cmi.2018.03.018
Koehler, M.; Aravamudhan, P.; Guzman-Cardozo, C.; Dumitru, A. C.; Yang, J.; Gargiulo, S.; Soumillion, P.; Dermody, T. S.; Alsteens, D. Glycan-Mediated Enhancement of Reovirus Receptor Binding. Nat. Commun. 2019, 10 ( 1), 1- 14, 10.1038/s41467-019-12411-2
Koehler, M.; Petitjean, S. J. L.; Yang, J.; Aravamudhan, P.; Somoulay, X.; Lo Giudice, C.; Poncin, M. A.; Dumitru, A. C.; Dermody, T. S.; Alsteens, D. Reovirus Directly Engages Integrin to Recruit Clathrin for Entry into Host Cells. Nat. Commun. 2021, 12 ( 1), 1- 15, 10.1038/s41467-021-22380-0
Newton, R.; Delguste, M.; Koehler, M.; Dumitru, A. C.; Laskowski, P. R.; Müller, D. J.; Alsteens, D. Combining Confocal and Atomic Force Microscopy to Quantify Single-Virus Binding to Mammalian Cell Surfaces. Nat. Protoc. 2017, 12 ( 11), 2275- 2292, 10.1038/nprot.2017.112
Liu, Z.; Moreira, R. A.; Dujmović, A.; Liu, H.; Yang, B.; Poma, A. B.; Nash, M. A. Mapping Mechanostable Pulling Geometries of a Therapeutic Anticalin/CTLA-4 Protein Complex. Nano Lett. 2022, 22 ( 1), 179- 187, 10.1021/acs.nanolett.1c03584
Zhu, R.; Canena, D.; Sikora, M.; Klausberger, M.; Seferovic, H.; Mehdipour, A. R.; Hain, L.; Laurent, E.; Monteil, V.; Wirnsberger, G.; Wieneke, R.; Tampé, R.; Kienzl, N. F.; Mach, L.; Mirazimi, A.; Oh, Y. J.; Penninger, J. M.; Hummer, G. Force-Tuned Avidity of Spike Variant-ACE2 Interactions Viewed on the Single- Molecule Level. Nat. Commun. 2022, 7926, 10.1038/s41467-022-35641-3
Robbiani, D. F.; Gaebler, C.; Muecksch, F.; Lorenzi, J. C. C.; Wang, Z.; Cho, A.; Agudelo, M.; Barnes, C. O.; Gazumyan, A.; Finkin, S.; Hägglöf, T.; Oliveira, T. Y.; Viant, C.; Hurley, A.; Hoffmann, H. H.; Millard, K. G.; Kost, R. G.; Cipolla, M.; Gordon, K.; Bianchini, F.; Chen, S. T.; Ramos, V.; Patel, R.; Dizon, J.; Shimeliovich, I.; Mendoza, P.; Hartweger, H.; Nogueira, L.; Pack, M.; Horowitz, J.; Schmidt, F.; Weisblum, Y.; Michailidis, E.; Ashbrook, A. W.; Waltari, E.; Pak, J. E.; Huey-Tubman, K. E.; Koranda, N.; Hoffman, P. R.; West, A. P.; Rice, C. M.; Hatziioannou, T.; Bjorkman, P. J.; Bieniasz, P. D.; Caskey, M.; Nussenzweig, M. C. Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals. Nature 2020, 584 ( 7821), 437- 442, 10.1038/s41586-020-2456-9
Sauer, M. M.; Tortorici, M. A.; Park, Y. J.; Walls, A. C.; Homad, L.; Acton, O. J.; Bowen, J. E.; Wang, C.; Xiong, X.; de van der Schueren, W.; Quispe, J.; Hoffstrom, B. G.; Bosch, B. J.; McGuire, A. T.; Veesler, D. Structural Basis for Broad Coronavirus Neutralization. Nat. Struct. Mol. Biol. 2021, 28 ( 6), 478- 486, 10.1038/s41594-021-00596-4
Wang, Z.; Muecksch, F.; Schaefer-Babajew, D.; Finkin, S.; Viant, C.; Gaebler, C.; Hoffmann, H. H.; Barnes, C. O.; Cipolla, M.; Ramos, V.; Oliveira, T. Y.; Cho, A.; Schmidt, F.; Da Silva, J.; Bednarski, E.; Aguado, L.; Yee, J.; Daga, M.; Turroja, M.; Millard, K. G.; Jankovic, M.; Gazumyan, A.; Zhao, Z.; Rice, C. M.; Bieniasz, P. D.; Caskey, M.; Hatziioannou, T.; Nussenzweig, M. C. Naturally Enhanced Neutralizing Breadth against SARS-CoV-2 One Year after Infection. Nature 2021, 595 ( 7867), 426- 431, 10.1038/s41586-021-03696-9
Dzimianski, J. V.; Lorig-Roach, N.; O’Rourke, S. M.; Alexander, D. L.; Kimmey, J. M.; DuBois, R. M. Rapid and Sensitive Detection of SARS-CoV-2 Antibodies by Biolayer Interferometry. Sci. Rep. 2020, 10 ( 1), 1- 12, 10.1038/s41598-020-78895-x
Barrows, J. K; Van Dyke, M. W. Biolayer Interferometry for DNA-Protein Interactions. PLoS One 2022, 17 ( 2), e0263322, 10.1371/journal.pone.0263322
Mannar, D.; Saville, J. W.; Zhu, X.; Srivastava, S. S.; Berezuk, A. M.; Tuttle, K. S.; Marquez, A. C.; Sekirov, I.; Subramaniam, S. SARS-CoV-2 Omicron Variant: Antibody Evasion and Cryo-EM Structure of Spike Protein-ACE2 Complex. Science (80-.). 2022, 375 ( 6582), 760- 764, 10.1126/science.abn7760
Hoffmann, M.; Zhang, L.; Pöhlmann, S. Omicron: Master of Immune Evasion Maintains Robust ACE2 Binding. Signal Transduct. Target. Ther. 2022, 7 ( 1), 2- 4, 10.1038/s41392-022-00965-5
Jalali, N.; Brustad, H. K.; Frigessi, A.; MacDonald, E. A.; Meijerink, H.; Feruglio, S. L.; Nygård, K. M.; Rø, G.; Madslien, E. H.; de Blasio, B. F. Increased Household Transmission and Immune Escape of the SARS-CoV-2 Omicron Compared to Delta Variants. Nat. Commun. 2022, 13 ( 1), 1- 5, 10.1038/s41467-022-33233-9
