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Cocktail of REGN Antibodies Binds More Strongly to SARS-CoV-2 Than Its Components, but the Omicron Variant Reduces Its Neutralizing Ability.
Nguyen, Hung; Lan, Pham Dang; Nissley, Daniel A; O'Brien, Edward P; Li, Mai Suan.
  • Nguyen H; Institute of Physics, Polish Academy of Sciences, al. Lotnikow 32/46, 02-668 Warsaw, Poland.
  • Lan PD; Life Science Lab, Institute for Computational Science and Technology, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, 729110 Ho Chi Minh City, Vietnam.
  • Nissley DA; Faculty of Physics and Engineering Physics, VNUHCM-University of Science, 227, Nguyen Van Cu Street, District 5, 749000 Ho Chi Minh City, Vietnam.
  • O'Brien EP; Department of Statistics, University of Oxford, Oxford Protein Bioinformatics Group, OX1 2JD Oxford, United Kingdom.
  • Li MS; Department of Chemistry, Penn State University, University Park, Pennsylvania 16802, United States.
J Phys Chem B ; 126(15): 2812-2823, 2022 04 21.
Article in English | MEDLINE | ID: covidwho-1783924
ABSTRACT
A promising approach to combat Covid-19 infections is the development of effective antiviral antibodies that target the SARS-CoV-2 spike protein. Understanding the structures and molecular mechanisms underlying the binding of antibodies to SARS-CoV-2 can contribute to quickly achieving this goal. Recently, a cocktail of REGN10987 and REGN10933 antibodies was shown to be an excellent candidate for the treatment of Covid-19. Here, using all-atom steered molecular dynamics and coarse-grained umbrella sampling, we examine the interactions of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with REGN10987 and REGN10933 separately as well as together. Both computational methods show that REGN10933 binds to RBD more strongly than REGN10987. Importantly, the cocktail binds to RBD (simultaneous binding) more strongly than its components. The dissociation constants of REGN10987-RBD and REGN10933-RBD complexes calculated from the coarse-grained simulations are in good agreement with the experimental data. Thus, REGN10933 is probably a better candidate for treating Covid-19 than REGN10987, although the cocktail appears to neutralize the virus more efficiently than REGN10933 or REGN10987 alone. The association of REGN10987 with RBD is driven by van der Waals interactions, while electrostatic interactions dominate in the case of REGN10933 and the cocktail. We also studied the effectiveness of these antibodies on the two most dangerous variants Delta and Omicron. Consistent with recent experimental reports, our results confirmed that the Omicron variant reduces the neutralizing activity of REGN10933, REGN10987, and REGN10933+REGN10987 with the K417N, N440K, L484A, and Q498R mutations playing a decisive role, while the Delta variant slightly changes their activity.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: J Phys Chem B Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jpcb.2c00708

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Topics: Variants Limits: Humans Language: English Journal: J Phys Chem B Journal subject: Chemistry Year: 2022 Document Type: Article Affiliation country: Acs.jpcb.2c00708