2. Academic Validation
  3. Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice

Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice

  • ACS Omega. 2022 Aug 29;7(36):31935-31944. doi: 10.1021/acsomega.2c02794.
Ana C Puhl 1,  Giovanni F Gomes 2,  Samara Damasceno 2,  Ethan J Fritch 3,  James A Levi 4,  Nicole J Johnson 4,  Frank Scholle 4,  Lakshmanane Premkumar 3,  Brett L Hurst 5 6,  Felipe Lee-Montiel 7,  Flavio P Veras 2,  Sabrina S Batah 8,  Alexandre T Fabro 8,  Nathaniel J Moorman 3 9 10,  Boyd L Yount 11,  Rebekah J Dickmander 3 9 10,  Ralph S Baric 3 9 11,  Kenneth H Pearce 10 12,  Fernando Q Cunha 2,  José C Alves-Filho 2,  Thiago M Cunha 2,  Sean Ekins 1
Affiliations

Affiliations

  • 1 Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, North Carolina 27606, United States.
  • 2 Center for Research in Inflammatory Diseases (CRID), Ribeirao Preto Medical School, University of Sao Paulo, Avenida Bandeirantes, 3900, Ribeirao Preto 14049-900, Sao Paulo, Brazil.
  • 3 Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, United States.
  • 4 Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695-7001, United States.
  • 5 Institute for Antiviral Research, Utah State University, Logan, Utah 84322-1400, United States.
  • 6 Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah 84322-1400, United States.
  • 7 PhenoVista Biosciences, 6195 Cornerstone Ct E. #114, San Diego, California 92121, United States.
  • 8 Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14090900, Brazil.
  • 9 Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States.
  • 10 Center for Integrative Chemical Biology and Drug Discovery, Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
  • 11 Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States.
  • 12 UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina 27599, United States.
PMID: 36097511 DOI: 10.1021/acsomega.2c02794
Abstract

The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising results on inhibition versus the toxic effect on A549-hACE2 cells (IC50 0.79 μM) while also showing a reduction of >3 log TCID50/mL for HCoV-229E. The in vivo efficacy of vandetanib was assessed in a mouse model of SARS-CoV-2 Infection and statistically significantly reduced the levels of IL-6, IL-10, and TNF-α and mitigated inflammatory cell infiltrates in the lungs of infected Animals but did not reduce viral load. Vandetanib also decreased CCL2, CCL3, and CCL4 compared to the infected Animals. Vandetanib additionally rescued the decreased IFN-1β caused by SARS-CoV-2 Infection in mice to levels similar to that in uninfected Animals. Our results indicate that the FDA-approved Anticancer drug vandetanib is worthy of further assessment as a potential therapeutic candidate to block the COVID-19 cytokine storm.

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