Binding of synthetic carbohydrate receptors to enveloped virus glycans: Insights from molecular dynamics simulations

Beicer Tapia; Genrietta Yagudayeva; M Fernando Bravo; Khushabu Thakur; Adam B Braunschweig; Mateusz Marianski

doi:10.1016/j.carres.2022.108574

Binding of synthetic carbohydrate receptors to enveloped virus glycans: Insights from molecular dynamics simulations

Carbohydr Res. 2022 Aug:518:108574. doi: 10.1016/j.carres.2022.108574. Epub 2022 May 8.

Authors

Beicer Tapia¹, Genrietta Yagudayeva², M Fernando Bravo², Khushabu Thakur³, Adam B Braunschweig⁴, Mateusz Marianski⁵

Affiliations

¹ Department of Chemistry and Biochemistry, Hunter College, The City University of New York, 695 Park Ave, New York, NY, 10065, USA; The PhD Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Ave, New York, NY, 10016, USA.
² Department of Chemistry and Biochemistry, Hunter College, The City University of New York, 695 Park Ave, New York, NY, 10065, USA.
³ Advanced Science Research Center of The City University of New York, 85 Nicolas Terrace, New York, NY, 10031, USA.
⁴ Department of Chemistry and Biochemistry, Hunter College, The City University of New York, 695 Park Ave, New York, NY, 10065, USA; The PhD Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Ave, New York, NY, 10016, USA; The PhD Program in Chemistry, The Graduate Center of The City University of New York, 365 5th Ave, New York, NY, 10016, USA; Advanced Science Research Center of The City University of New York, 85 Nicolas Terrace, New York, NY, 10031, USA.
⁵ Department of Chemistry and Biochemistry, Hunter College, The City University of New York, 695 Park Ave, New York, NY, 10065, USA; The PhD Program in Biochemistry, The Graduate Center of The City University of New York, 365 5th Ave, New York, NY, 10016, USA; The PhD Program in Chemistry, The Graduate Center of The City University of New York, 365 5th Ave, New York, NY, 10016, USA; Advanced Science Research Center of The City University of New York, 85 Nicolas Terrace, New York, NY, 10031, USA. Electronic address: mmarians@hunter.cuny.edu.

Abstract

Can envelope glycans be targeted to stop viral pandemics? Here we address this question by using molecular dynamics simulations to study the binding between 10 synthetic carbohydrate receptors (SCRs) and the 33 N-glycans most commonly found on the surfaces of enveloped viruses, including Zika virus and SARS-CoV-2. Based on association quotients derived from these simulations, we classified the SCRs as weak binders, promiscuous binders, or selective binders. The SCRs almost exclusively associate at the Man₃GlcNAc₂ core, which is common to all N-glycans, but the binding affinity between the SCR⋅glycan pair depends on the noncovalent interactions between the heterocycle rings and the glycan antennae. Systematic variations in the glycan and SCR structures reveal relationships that could guide the design of SCRs to attain affinity and selectivity towards a chosen envelope glycan target. With these results, envelope glycans, which are currently considered "undruggable", could become viable targets for new therapeutic strategies.

Keywords: Antiviral agents; Glycans; Molecular dynamics simulations; Supramolecular chemistry; Viruses.

MeSH terms

COVID-19*
Carbohydrates / chemistry
Humans
Molecular Dynamics Simulation
Polysaccharides / chemistry
Receptors, Artificial* / chemistry
SARS-CoV-2
Zika Virus Infection*
Zika Virus* / metabolism

Substances

Carbohydrates
Polysaccharides
Receptors, Artificial

Grants and funding

SC2 GM135145/GM/NIGMS NIH HHS/United States