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How the Universal MSA52 Aptamer Recognizes the SARS-CoV‑2 Spike Protein.
Tadsanee Awang1, Firdaus Samsudin2, Deanpen Japrung3
1Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand.
ACS Omega
|October 13, 2025
Summary
A universal aptamer (MSA52) binds the SARS-CoV-2 spike protein, targeting conserved regions for broad variant recognition. Molecular dynamics simulations reveal distinct binding modes in glycosylated and nonglycosylated forms, offering insights for aptamer-based biosensor design.
Area of Science:
- Structural biology and virology
- Biochemistry and molecular dynamics
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes its spike (S) glycoprotein for host cell entry, making it a key target for therapeutics and vaccines.
- A universal aptamer, MSA52, has shown binding to the S protein across seven former variants of concern (VOCs) in both glycosylated and nonglycosylated states.
- Limited molecular-level understanding exists regarding the interaction between MSA52 and the SARS-CoV-2 S protein.
Purpose of the Study:
- To elucidate the molecular interactions between the MSA52 aptamer and the SARS-CoV-2 S protein using molecular dynamics (MD) simulations.
- To investigate the binding characteristics of MSA52 in both nonglycosylated (NG) and glycosylated (G) forms of the S protein.
Main Methods:
- Molecular dynamics (MD) simulations were employed to model and analyze the binding of MSA52 to the NG and G forms of the SARS-CoV-2 S protein.
- Analysis focused on identifying key interaction sites, binding modes, and the forces driving the aptamer-protein complex formation.
Main Results:
- In the NG form, MSA52 binds between the receptor binding domain (RBD) and N-terminal domain (NTD) of the S protein.
- In the G form, MSA52 primarily interacts with the RBD, with contributions from both protein and glycan components.
- Binding is predominantly driven by electrostatic interactions, with MSA52 showing tighter binding to the NG form and recognizing a conserved region across VOCs, enabling binding to both RBD-up and RBD-down conformations.
Conclusions:
- MSA52 exhibits distinct binding mechanisms depending on the glycosylation state of the SARS-CoV-2 S protein, primarily engaging the RBD in conserved regions.
- The aptamer's ability to bind both glycosylated and nonglycosylated S proteins, as well as different RBD conformations, highlights its potential for broad-spectrum antiviral applications.
- These molecular insights are crucial for the rational design of advanced SARS-CoV-2 aptamer-based biosensors and therapeutic strategies.
