2. Academic Validation
  3. Bioassay-guided Isolation of SARS-CoV-2 Viral Entry Inhibitors From the Brown Algae Lobophora variegata Identifies Fucoxanthin as a Selective ACE-2/Spike Inhibitor

Bioassay-guided Isolation of SARS-CoV-2 Viral Entry Inhibitors From the Brown Algae Lobophora variegata Identifies Fucoxanthin as a Selective ACE-2/Spike Inhibitor

  • Chem Biodivers. 2025 Aug 29:e01403. doi: 10.1002/cbdv.202501403.
Victoria M Casimir-Montán 1,  Marie L Matos-Hernández 2,  Adrián González-Bravo 3,  Edwin A Hernández-Delgado 3 4 5 6,  Grayce Dyer 2,  Joseph M Salvino 7,  Luis J Montaner 7,  Joel A Cassel 7,  Troy E Messick 7,  Ian Tietjen 7,  Eduardo J E Caro-Diaz 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Natural Sciences College, University of Puerto Rico - Rio Piedras Campus, San Juan, Puerto Rico, USA.
  • 2 Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico - Medical Sciences Campus, San Juan, Puerto Rico, USA.
  • 3 Interdisciplinary Program, Natural Sciences College, University of Puerto Rico - Rio Piedras Campus, San Juan, Puerto Rico, USA.
  • 4 Department of Environmental Sciences, Natural Sciences College, University of Puerto Rico - Rio Piedras Campus, San Juan, Puerto Rico, USA.
  • 5 Center For Applied Tropical Ecology and Conservation, University of Puerto Rico - Rio Piedras Campus, San Juan, Puerto Rico, USA.
  • 6 Sociedad Ambiente Marino, San Juan, Puerto Rico, USA.
  • 7 The Wistar Institute, Philadelphia, Pennsylvania, USA.
PMID: 40882140 DOI: 10.1002/cbdv.202501403
Abstract

The continual emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, as well as unwanted side effects, limited worldwide availability, and risk of drug resistance from approved antivirals, continue to limit the effectiveness of coronavirus disease 2019 treatment. To continue to uncover natural products (NPs) that can inhibit validated biochemical targets of coronaviruses, we focused on a subset of brown algae extracts from Puerto Rico that demonstrated potential anti-SARS-CoV-2 activity through selective disruption of the viral Spike-receptor binding domain (RBD) to the host angiotensin-converting enzyme-2 (ACE2) cellular entry receptor, which in turn led to further evaluation of a Lobophora variegata organic extract. Employing bioassay-guided fractionation and modern NPs dereplication tools, we quickly identified fucoxanthin as an active constituent with selective inhibitory activity against spike-RBD/ACE-2 binding while also exhibiting moderate potency in vitro toward pseudo-virus-infected VERO cells. Preliminary in silico docking demonstrated that fucoxanthin binds stably at the RBD-spike protein interface and has provided a hypothesized binding site for further chemical and biological studies.

Keywords

COVID‐19; SARS‐CoV‐2; antiviral agents; marine natural products.

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