Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants

Melanie Koehler; Ankita Ray; Rodrigo A. Moreira; Blinera Juniku; Adolfo B. Poma; David Alsteens

doi:10.1038/s41467-021-27325-1

Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants

Melanie Koehler (Shared First Author), Ankita Ray (Shared First Author), Rodrigo A. Moreira (Co-Author), Blinera Juniku (Co-Author), Adolfo B. Poma^* (Co-Author), David Alsteens^* (Last Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

689 Scopus citations

Abstract

Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.

Original language	English
Article number	6977
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27325-1
State	Published - Dec 2021
Externally published	Yes

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title = "Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants",

abstract = "Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.",

author = "Melanie Koehler and Ankita Ray and Moreira, \{Rodrigo A.\} and Blinera Juniku and Poma, \{Adolfo B.\} and David Alsteens",

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AU - Koehler, Melanie

AU - Ray, Ankita

AU - Moreira, Rodrigo A.

AU - Juniku, Blinera

AU - Poma, Adolfo B.

AU - Alsteens, David

PY - 2021/12

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N2 - Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.

AB - Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD—ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD—ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.

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Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants

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