Curious Binding Energy Increase between the Receptor-Binding Domain of the SARS-CoV‑2 Spike Protein and Angiotensin-Converting Enzyme 2 Adsorbed on a Silane Monolayer from Molecular Dynamics Simulations

• Published in: The journal of physical chemistry. B Vol. 125; no. 39; pp. 11078 - 11090
• Main Authors: Lecot, Solène, Chevolot, Yann, Phaner-Goutorbe, Magali, Yeromonahos, Christelle
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07.10.2021
• Subjects: adsorption; Angiotensin-Converting Enzyme 2; B: Soft Matter, Fluid Interfaces, Colloids, Polymers, and Glassy Materials; bioactive properties; Biochemistry, Molecular Biology; Chemical Sciences; COVID-19; COVID-19 infection; energy; Gibbs free energy; Humans; hydrogen; Life Sciences; Microbiology and Parasitology; molecular dynamics; Molecular Dynamics Simulation; mutation; or physical chemistry; peptidyl-dipeptidase A; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; silane; Silanes; Spike Glycoprotein, Coronavirus - genetics; Theoretical and; Virology; viruses
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/acs.jpcb.1c06050

In the context of the COVID-19 outbreak since December 2019, antigenic tests are widely used, for diagnosis purposes, to detect the SARS-CoV-2 spike protein in nasopharyngeal fluid through its interactions with specific antibodies. However, the SARS-CoV-2 spike protein is subject to rapid mutations yielding more and more variants that might lose their affinity toward the currently used antibodies. The virus entry into the host cell involves interactions between the angiotensin-converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein receptor-binding domain. Consequently, ACE2 could be a target with limited mutation escaping possibilities. However, as the enzyme has not evolved to recognize the virus, its affinity with the spike protein receptor-binding domain is lower than that with specific antibodies. The present molecular dynamics simulations study suggests that the adsorption of the ACE2 on specific silane monolayers could increase its affinity toward the spike protein receptor-binding domain. Indeed, silane monolayers, combining silane molecules with short alkyl chains and positively charged head groups and silane molecules without charged head groups, could adsorb the ACE2 while maintaining its bioactivity (orientation compatible with the spike protein trapping, low conformational changes) and increasing its interactions with the spike protein receptor-binding domain (number of hydrogen bonds and electrostatic interactions) to lead to an increase by 20% both in the binding free energy and in the enzyme /receptor-binding domain rupture force. This work could help develop biosensing tools efficient toward any variants of the SARS-CoV-2 spike protein.