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

Author:

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

Abstract

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.

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Reference34 articles.

1. https://www.who.int/news-room/fact-sheets/detail/hiv-aids

2. The Effects of the COVID-19 Pandemic on the HIV Responsehttps://www.unaids.org/en/resources/documents/2021/effects-of-covid19-pandemic-on-hiv-response

3. Does lopinavir really inhibit SARS-CoV-2?

4. Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials

5. Hydroxychloroquine and Remdesivir in COVID-19: A critical analysis of recent events

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