Research output: Contribution to journal › Article › peer-review
Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses. / Fomenko, Vladislav V.; Rudometova, Nadezhda B.; Yarovaya, Olga I. et al.
In: Molecules, Vol. 27, No. 1, 295, 01.01.2022.Research output: Contribution to journal › Article › peer-review
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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 -
ID: 35167213