TY - JOUR

T1 - Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses

AU - Fomenko, Vladislav V.

AU - Rudometova, Nadezhda B.

AU - Yarovaya, Olga I.

AU - Rogachev, Artem D.

AU - Fando, Anastasia A.

AU - Zaykovskaya, Anna V.

AU - Komarova, Nina I.

AU - Shcherbakov, Dmitry N.

AU - Pyankov, Oleg V.

AU - Pokrovsky, Andrey G.

AU - Karpenko, Larisa I.

AU - Maksyutov, Rinat A.

AU - Salakhutdinov, Nariman F.

N1 - Funding Information: Funding: Chemical synthesis of glycyrrhizinic acid derivatives was funded by the Ministry of Science and Higher Education of the Russian Federation in the implementation of the research program “Use of synchrotron radiation for virological research” within the framework of the Federal Scientific and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure for 2019–2027 (Agreement No. 075-15-2021-1355 (12 October 2021)). The study of antiviral activity of the compounds was conducted under the state assignment of FBRI SRC VB “Vector”, Rospotrebnadzor. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri-and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC50 2–8 µM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC50 range 3.9–27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action.

AB - When developing drugs against SARS-CoV-2, it is important to consider the characteristics of patients with different co-morbidities. People infected with HIV-1 are a particularly vulnerable group, as they may be at a higher risk than the general population of contracting COVID-19 with clinical complications. For such patients, drugs with a broad spectrum of antiviral activity are of paramount importance. Glycyrrhizinic acid (Glyc) and its derivatives are promising biologically active compounds for the development of such broad-spectrum antiviral agents. In this work, derivatives of Glyc obtained by acylation with nicotinic acid were investigated. The resulting preparation, Glycyvir, is a multi-component mixture containing mainly mono-, di-, tri-and tetranicotinates. The composition of Glycyvir was characterized by HPLC-MS/MS and its toxicity assessed in cell culture. Antiviral activity against three strains of SARS-CoV-2 was tested in vitro on Vero E6 cells by MTT assay. Glycyvir was shown to inhibit SARS-CoV-2 replication in vitro (IC50 2–8 µM) with an antiviral activity comparable to the control drug Remdesivir. In addition, Glycyvir exhibited marked inhibitory activity against HIV pseudoviruses of subtypes B, A6 and the recombinant form CRF63_02A (IC50 range 3.9–27.5 µM). The time-dependence of Glycyvir inhibitory activity on HIV pseudovirus infection of TZM-bl cells suggested that the compound interfered with virus entry into the target cell. Glycyvir is a promising candidate as an agent with low toxicity and a broad spectrum of antiviral action.

KW - Entry inhibitors

KW - Human immunodeficiency virus type 1

KW - Nicotinates of glycyrrhizic acid

KW - SARS-CoV-2

KW - Chlorocebus aethiops

KW - COVID-19/drug therapy

KW - Antiviral Agents/chemical synthesis

KW - Glycyrrhizic Acid/chemistry

KW - Humans

KW - SARS-CoV-2/drug effects

KW - HIV Infections/drug therapy

KW - HIV-1/drug effects

KW - Animals

KW - Virus Replication

KW - HeLa Cells

KW - In Vitro Techniques

KW - Vero Cells

UR - http://www.scopus.com/inward/record.url?scp=85122243186&partnerID=8YFLogxK

U2 - 10.3390/molecules27010295

DO - 10.3390/molecules27010295

M3 - Article

C2 - 35011529

AN - SCOPUS:85122243186

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 1

M1 - 295

ER -