Antiviral activity of natural humic substances and shilajit materials against HIV-1: Relation to structure

Yury V Zhernov; Andrey I Konstantinov; Alexander Zherebker; Eugene Nikolaev; Alexey Orlov; Mikhail I Savinykh; Galina V Kornilaeva; Eduard V Karamov; Irina V Perminova

doi:10.1016/j.envres.2020.110312

Antiviral activity of natural humic substances and shilajit materials against HIV-1: Relation to structure

Environ Res. 2021 Feb:193:110312. doi: 10.1016/j.envres.2020.110312. Epub 2020 Oct 14.

Authors

Yury V Zhernov¹, Andrey I Konstantinov², Alexander Zherebker³, Eugene Nikolaev³, Alexey Orlov³, Mikhail I Savinykh⁴, Galina V Kornilaeva⁵, Eduard V Karamov⁵, Irina V Perminova⁶

Affiliations

¹ National Research Center - Institute of Immunology FMBA of Russia, Moscow, 115522, Russia.
² Lomonosov Moscow State University, Department of Chemistry, Moscow, 119991, Russia.
³ Skolkovo Institute of Science and Technology, Skolkovo, Moscow Region, 143026, Russia.
⁴ Scientific and Production Company "Sibdalmumiyo" Ltd., Novokuznetsk, Russia.
⁵ D.I. Ivanovsky Institute of Virology FSBI «National Research Center for Epidemiology and Microbiology Named After the Honorary Academician N.F. Gamaleya», Moscow, 123098, Russia.
⁶ Lomonosov Moscow State University, Department of Chemistry, Moscow, 119991, Russia. Electronic address: iperm@org.chem.msu.ru.

Abstract

Natural products, such as humic substances (HS) and shilajit, are known to possess antiviral activity. Humic-like components are often called as carriers of biological activity of shilajit. The goal of this study was to evaluate anti-HIV activity of well characterized HS isolated from coal, peat, and peloids, and compare it to that of water-soluble organic matter (OM) isolated from different samples of Shilajit. The set of humic materials included 16 samples of different fractional composition: humic acid (HA), hymatomelanic acid (HMA), fulvic acid (FA). The set of shilajit OM included 19 samples of different geographic origin and level of alteration. The HIV-1 p24 antigen assay and cell viability test were used for assessment of antiviral activity. The HIV-1 Bru strain was used to infect CEM-SS cells. The obtained EC50 values varied from 0.37 to 1.4 mg L^-1 for the humic materials, and from 14 to 142 mg L^-1 for the shilajit OM. Hence, all humic materials used in this study outcompeted largely the shilajit materials with respect to anti-HIV activity: For the humic materials, the structure-activity relationships revealed strong correlation between the EC50 values and the content of aromatic carbon indicating the most important role of aromatic structures. For shilajit OM, the reverse relationship was obtained indicating the different mechanism of shilajit activity. The FTICRMS molecular assignments were used for ChEMBL data mining in search of the active humic molecules. As potential carriers of antiviral activity were identified aromatic structures with alkyl substituents, terpenoids, N-containing analogs of typical flavonoids, and aza-podophyllotoxins. The conclusion was made that the typical humic materials and Shilajit differ greatly in molecular composition, and the humic materials have substantial preferences as a natural source of antiviral agents as compared to shilajit.

Keywords: (13)C NMR; Antiviral; ChemBL data-mining; FTICR MS; Fulvic acid; HIV; Humic acid; Shilajit; Structure-activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
Benzopyrans / pharmacology
HIV-1*
Humic Substances* / analysis
Minerals
Resins, Plant
Soil

Substances

Antiviral Agents
Benzopyrans
Humic Substances
Minerals
Resins, Plant
Soil
mumie