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
  • 1. Ufa Institute of Chemistry UFRC RAS, pr. Oktyabrya 71, 450054, Ufa, Russia. [email protected].
  • 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. [email protected].
  • 7. Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, 518132, China. [email protected].
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.

Products