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

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

Journal

Molecules
, E-ISSN: 1420-3049

Output data

Year: 2022, Volume: 27, Number: 1, Article number : 295, Pages count : DOI: 10.3390/molecules27010295

Tags

Entry inhibitors; Human immunodeficiency virus type 1; Nicotinates of glycyrrhizic acid; SARS-CoV-2

Authors

Fomenko Vladislav V. ¹ , Rudometova Nadezhda B. ² , Yarovaya Olga I. ^1,3 , Rogachev Artem D. ¹ , Fando Anastasia A. ³ , Zaykovskaya Anna V. ² , Komarova Nina I. ¹ , Shcherbakov Dmitry N. ² , Pyankov Oleg V. ² , Pokrovsky Andrey G. ³ , Karpenko Larisa I. ² , Maksyutov Rinat A. ² , Salakhutdinov Nariman F. ^1,3

Affiliations

1	Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, Novosibirsk, 630090, Russian Federation
2	State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, 630559, Russian Federation
3	Zelman Institute for Medicine and Psychology, Novosibirsk State University, Pirogov Str. 1, Novosibirsk, 630090, Russian Federation

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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Fomenko V.V. , Rudometova N.B. , Yarovaya O.I. , Rogachev A.D. , Fando A.A. , Zaykovskaya A.V. , Komarova N.I. , Shcherbakov D.N. , Pyankov O.V. , Pokrovsky A.G. , Karpenko L.I. , Maksyutov R.A. , Salakhutdinov N.F.
Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses
Molecules. 2022. V.27. N1. 295 . DOI: 10.3390/molecules27010295 WOS Scopus

Web of science	WOS:000751037100001
Scopus	2-s2.0-85122243186
OpenAlex	W4205765404