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

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

doi:10.3390/molecules27010295

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.

Highlights

In the spring of 2020, the world was confronted with a fundamentally new type of threat—a global pandemic of the coronavirus infection COVID-19
ChemistryglycyIrnrhtheitsicreapcoidrts, we present and of our the results of experiments our preparation of on their antiviral nicotinates glycyrrhizic and activity against both HIV-1
This mixture—which we named Glycivir—is depicted in general terms inGlFyicgyurrreh2iz.iMniocdaecridn iasniasloyltaicteadl mfreotmhondastuwrearlesothuernceesmthpalot ycoednttaoinanreallaytzeed saponins in this mixture iandadnitiaotntetmopittstmo haianrnceosms pthoeneconmt, Gplleyxcitiytseolff.suTchhe apnraoldyuscets.we obtained in our synthesis is a multi-compound mixture of Glycyrrhizinic acid (Glyc)-based derivatives containing Glyc nicotinates, mainly mono, di, tri- and tetranicotinates

Summary

Introduction

In the spring of 2020, the world was confronted with a fundamentally new type of threat—a global pandemic of the coronavirus infection COVID-19. It is not the first pandemic in human history, in some respects it differs significantly from all previous pandemics, in particular in its global impact on the economy and the politics of every country in the world. The development of vaccines and effective therapeutics is a major undertaking of the global scientific community, at an unprecedented scale. Effective vaccines against SARSCoV-2 are available, they are likely to become less effective with the emergence of new mutant variants, prompting new vaccine development efforts. Progress in the identification of effective therapeutics has been much more modest, with no drug universally recognized as effective against SARS-CoV-2

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Conclusion