Synthetic Analogs of the Sponge Sesterterpenoid Alotaketal C are Potent Inhibitors of SARS-CoV-2 Omicron BA.1 and BA.5 Infections of Human Lung Cells

  • Org Lett. 2023 Jul 7;25(26):4825-4829. doi: 10.1021/acs.orglett.3c01536.
Polina Blagojevic  1 ,  Jimena Perez-Vargas  2 ,  Kunzhong Jian  1 ,  David E Williams  1 ,  Ivan Villanueva  2 ,  Connor A H Thompson  2 ,  Siobhan Ennis  3 ,  Masahiro Niikura  3 ,  Ian Tietjen  4 ,  François Jean  2 ,  Raymond J Andersen  1
Affiliations
  • 1. Departments of Chemistry and Earth, Ocean & Atmospheric Science, University of British Columbia, Vancouver, BC, V6T 1Z1, Canada.
  • 2. Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
  • 3. Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
  • 4. The Wistar Institute, Philadelphia, Pennsylvania, 19104, United States.
PMID: 37358030 DOI: 10.1021/acs.orglett.3c01536
Abstract

The protein kinase C-activating Sponge natural product alotaketal C (1) potently inhibits the Infection of human Calu-3 lung cells by SARS-CoV-2 Omicron BA.1 and BA.5 variants. Simplified analogs of 1 have been synthesized and tested for anti-SARS-CoV-2 activity providing SAR data for the Antiviral pharmacophore of 1. Analogs 19 and 23, which are missing the C-11 substituents in 1 and have modified C-13 appendages, are ∼2- to 7-fold more potent than 1 and have equal or larger selectivity indices.

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