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Evaluation of A-ring hydroxymethylene-amino- triterpenoids as inhibitors of SARS-CoV-2 spike pseudovirus and influenza H1N1

The Journal of Antibiotics volume 77, pages 39–49 (2024)Cite this article

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Abstract

A set of triterpene A-ring hydroxymethylene-amino-derivatives was synthesized and their antiviral activity was studied. The synthesized compounds were tested for their potential inhibition of SARS-CoV-2 pseudovirus in BHK-21-hACE2 cells and influenza A/PuertoRico/8/34 (H1N1) virus in MDCK cell culture. Compounds 6, 8 and 19 showed significant anti-SARS-CoV-2 pseudovirus activity with EC50 value of 3.20-11.13 µM, which is comparable to the positive control amodiaquine (EC50 3.17 µM). Among them, 28-O-imidazolyl-azepano-betulin 6 and C3-hydroxymethylene-amino-glycyrrhetol-11,13-diene 19 were identified as the lead compounds with SI values of 7 and 10. The binding mode of compound 6 into the RBD domain of SARS-CoV-2 spike glycoprotein (PDB code: 7DK3) by docking and molecular dynamics simulation was investigated.

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Funding

This research was funded by RFBR and NSFC according to the research project № 20-53-55001 and the International Cooperation and Exchange Program of China (NSFC-RFBR, No. 82161148006).

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Authors and Affiliations

  1. Ufa Institute of Chemistry UFRC RAS, pr. Oktyabrya 71, 450054, Ufa, Russia

    Oxana Kazakova, Elena Tretyakova & Irina Smirnova

  2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Xinyuan Ma, Hongwei Jin, Demin Zhou & Sulong Xiao

  3. Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, 518132, China

    Xinyuan Ma, Demin Zhou & Sulong Xiao

  4. Department of Virology, St. Petersburg Pasteur Institute of Epidemiology and Microbiology, Experimental Virology Laboratory, 14 Mira St., St. Petersburg, 197001, Russia

    Alexander Slita, Ekaterina Sinegubova & Vladimir Zarubaev

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Kazakova, O., Ma, X., Tretyakova, E. et al. Evaluation of A-ring hydroxymethylene-amino- triterpenoids as inhibitors of SARS-CoV-2 spike pseudovirus and influenza H1N1. J Antibiot 77, 39–49 (2024). https://doi.org/10.1038/s41429-023-00677-0

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