2. Academic Validation
  3. 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

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

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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