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

Molecules

卷:27

Olga I. Yarovaya¹  Nina I. Komarova¹  Nariman F. Salakhutdinov¹  Artem D. Rogachev¹  Vladislav V. Fomenko¹  Anna V. Zaykovskaya²  Oleg V. Pyankov²  Dmitry N. Shcherbakov²  Nadezhda B. Rudometova²  Larisa I. Karpenko²  Rinat A. Maksyutov²  Andrey G. Pokrovsky³  Anastasia A. Fando³ 

[1] Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia;

[2] State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia;

[3] Zelman Institute for Medicine and Psychology, Novosibirsk State University, Pirogov Str. 1, 630090 Novosibirsk, Russia;

关键词: human immunodeficiency virus type 1;    SARS-CoV-2;    entry inhibitors;    nicotinates of glycyrrhizic acid;   

DOI  :  10.3390/molecules27010295

来源: DOAJ

【 摘 要 】

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 (IC₅₀2–8 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.

【 授权许可】

Unknown