The mutual lipid-mediated effect of the transmembrane domain of SARS-CoV-2 E-protein and glycyrrhizin nicotinate derivatives on the localization in the lipid bilayer

Polina A Kononova; Olga Yu Selyutina; Vladislav V Fomenko; Nariman F Salakhutdinov; Nikolay E Polyakov

doi:10.1016/j.abb.2024.110080

The mutual lipid-mediated effect of the transmembrane domain of SARS-CoV-2 E-protein and glycyrrhizin nicotinate derivatives on the localization in the lipid bilayer

Arch Biochem Biophys. 2024 Aug:758:110080. doi: 10.1016/j.abb.2024.110080. Epub 2024 Jul 2.

Authors

Polina A Kononova¹, Olga Yu Selyutina², Vladislav V Fomenko³, Nariman F Salakhutdinov⁴, Nikolay E Polyakov⁵

Affiliations

¹ V. V. Voevodsky Institute of Chemical Kinetics and Combustion, 3 Institutskaya St., 630090, Novosibirsk, Russia.
² V. V. Voevodsky Institute of Chemical Kinetics and Combustion, 3 Institutskaya St., 630090, Novosibirsk, Russia; Institute of Solid State Chemistry and Mechanochemistry, 18 Kutateladze St., 630128, Novosibirsk, Russia. Electronic address: [email protected].
³ V. V. Voevodsky Institute of Chemical Kinetics and Combustion, 3 Institutskaya St., 630090, Novosibirsk, Russia; N. N. Vorozhtsov Institute of Organic Chemistry, 9 Lavrentiev Ave, 630090, Novosibirsk, Russia.
⁴ N. N. Vorozhtsov Institute of Organic Chemistry, 9 Lavrentiev Ave, 630090, Novosibirsk, Russia.
⁵ V. V. Voevodsky Institute of Chemical Kinetics and Combustion, 3 Institutskaya St., 630090, Novosibirsk, Russia; Institute of Solid State Chemistry and Mechanochemistry, 18 Kutateladze St., 630128, Novosibirsk, Russia.

PMID: 38960345
DOI: 10.1016/j.abb.2024.110080

Abstract

Glycyrrhizinic acid (GA) is one of the active substances in licorice root. It exhibits antiviral activity against various enveloped viruses, for example, SARS-CoV-2. GA derivatives are promising biologically active compounds from perspective of developing broad-spectrum antiviral agents. Given that GA nicotinate derivatives (Glycyvir) demonstrate activity against various DNA- and RNA-viruses, a search for a possible mechanism of action of these compounds is required. In the present paper, the interaction of Glycyvir with the transmembrane domain of the SARS-CoV-2 E-protein (ETM) in a model lipid membrane was investigated by NMR spectroscopy and molecular dynamics simulation. The lipid-mediated influence on localization of the SARS-CoV-2 E-protein by Glycyvir was observed. The presence of Glycyvir leads to deeper immersion of the ETM in lipid bilayer. Taking into account that E-protein plays a significant role in virus production and takes part in virion assembly and budding, the data on the effect of potential antiviral agents on ETM localization and structure in the lipid environment may provide a basis for further studies of potential coronavirus E-protein inhibitors.

Keywords: Antiviral activity; Coronavirus E-protein; Glycyvir; Lipid membranes; Molecular dynamics; NMR; Nicotinates of glycyrrhizinic acid; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents* / chemistry
Antiviral Agents* / pharmacology
COVID-19 Drug Treatment
Coronavirus Envelope Proteins / chemistry
Coronavirus Envelope Proteins / metabolism
Glycyrrhizic Acid* / chemistry
Glycyrrhizic Acid* / pharmacology
Humans
Lipid Bilayers* / chemistry
Lipid Bilayers* / metabolism
Molecular Dynamics Simulation*
Protein Domains
SARS-CoV-2* / drug effects
SARS-CoV-2* / metabolism

Substances

Lipid Bilayers
Glycyrrhizic Acid
Antiviral Agents
Coronavirus Envelope Proteins
envelope protein, SARS-CoV-2