2. Academic Validation
  3. Modulation of in Vitro SARS-CoV-2 Infection by Stephania tetrandra and Its Alkaloid Constituents

Modulation of in Vitro SARS-CoV-2 Infection by Stephania tetrandra and Its Alkaloid Constituents

  • J Nat Prod. 2023 Apr 28;86(4):1061-1073. doi: 10.1021/acs.jnatprod.3c00159.
Aswad Khadilkar 1,  Zoie L Bunch 2,  Jessica Wagoner 3,  Vandana Ravindran 4,  Jessica M Oda 3,  Warren S Vidar 2,  Trevor N Clark 5,  Preston K Manwill 2,  Daniel A Todd 2,  Sarah A Barr 6,  Lauren K Olinger 7,  Susan L Fink 3,  Wendy K Strangman 6,  Roger G Linington 5,  John B MacMillan 1,  Nadja B Cech 2,  Stephen J Polyak 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95964, United States.
  • 2 Department of Chemistry and Biochemistry, University of North Carolina, Greensboro, North Carolina 27412, United States.
  • 3 Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington 98195,United States.
  • 4 Oslo Centre for Biostatistics and Epidemiology (OCBE), Faculty of Medicine, University of Oslo, Oslo 0313, Norway.
  • 5 Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
  • 6 Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28403, United States.
  • 7 Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, North Carolina 28403, United States.
PMID: 37043739 DOI: 10.1021/acs.jnatprod.3c00159
Abstract

Botanical Natural Products have been widely consumed for their purported usefulness against COVID-19. Here, six botanical species from multiple sources and 173 isolated natural product compounds were screened for blockade of wild-type (WT) SARS-CoV-2 Infection in human 293T epithelial cells overexpressing ACE-2 and TMPRSS2 protease (293TAT). Antiviral activity was demonstrated by an extract from Stephania tetrandra. Extract fractionation, liquid chromatography-mass spectrometry (LC-MS), Antiviral assays, and computational analyses revealed that the alkaloid fraction and purified Alkaloids tetrandrine, fangchinoline, and cepharanthine inhibited WT SARS-CoV-2 Infection. The Alkaloids and alkaloid fraction also inhibited the delta variant of concern but not WT SARS-CoV-2 in VeroAT cells. Membrane permeability assays demonstrate that the Alkaloids are biologically available, although fangchinoline showed lower permeability than tetrandrine. At high concentrations, the extract, alkaloid fractions, and pure Alkaloids induced phospholipidosis in 293TAT cells and less so in VeroAT cells. Gene expression profiling during virus Infection suggested that alkaloid fraction and tetrandrine displayed similar effects on cellular gene expression and pathways, while fangchinoline showed distinct effects on cells. Our study demonstrates a multifaceted approach to systematically investigate the diverse activities conferred by complex botanical mixtures, their cell-context specificity, and their pleiotropic effects on biological systems.

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