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

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

  • J Antibiot (Tokyo). 2024 Jan;77(1):39-49. doi: 10.1038/s41429-023-00677-0.
Oxana Kazakova 1,  Xinyuan Ma 2 3,  Elena Tretyakova 4,  Irina Smirnova 4,  Alexander Slita 5,  Ekaterina Sinegubova 5,  Vladimir Zarubaev 5,  Hongwei Jin 2,  Demin Zhou 2 3,  Sulong Xiao 6 7
Affiliations

Affiliations

  • 1 Ufa Institute of Chemistry UFRC RAS, pr. Oktyabrya 71, 450054, Ufa, Russia. obf@anrb.ru.
  • 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
  • 3 Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
  • 4 Ufa Institute of Chemistry UFRC RAS, pr. Oktyabrya 71, 450054, Ufa, Russia.
  • 5 Department of Virology, St. Petersburg Pasteur Institute of Epidemiology and Microbiology, Experimental Virology Laboratory, 14 Mira St., St. Petersburg, 197001, Russia.
  • 6 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. slxiao@bjmu.edu.cn.
  • 7 Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, 518132, China. slxiao@bjmu.edu.cn.
PMID: 38001284 DOI: 10.1038/s41429-023-00677-0
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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