Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air–Liquid Interface Cultured Human Primary Bronchial Epithelial Cells
Bram M. ter Ellen,
Nilima Dinesh Kumar,
Ellen M. Bouma,
Berit Troost,
Denise P.I. van de Pol,
Heidi H. van der Ende-Metselaar,
Leonie Apperloo,
Djoke van Gosliga,
Maarten van den Berge,
Martijn C. Nawijn,
Peter H.J. van der Voort,
Jill Moser,
Izabela A. Rodenhuis-Zybert,
Jolanda M. Smit
Affiliations
Bram M. ter Ellen
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Nilima Dinesh Kumar
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Ellen M. Bouma
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Berit Troost
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Denise P.I. van de Pol
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Heidi H. van der Ende-Metselaar
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Leonie Apperloo
Department of Pathology and Medical Biology, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Djoke van Gosliga
Department of Pediatrics, Beatrix Children’s Hospital, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Maarten van den Berge
Department of Pulmonary Diseases, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Martijn C. Nawijn
Department of Pathology and Medical Biology, GRIAC Research Institute, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Peter H.J. van der Voort
Department of Critical Care, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Jill Moser
Department of Critical Care, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Izabela A. Rodenhuis-Zybert
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Jolanda M. Smit
Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health and economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, and antioxidant properties as an advantageous antiviral therapy for SARS-CoV-2 infection. Here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, exhibit potent antiviral properties against SARS-CoV-2 in vitro. First, we show that resveratrol and pterostilbene antiviral activity in African green monkey kidney cells. Both compounds actively inhibit virus replication within infected cells as reduced virus progeny production was observed when the compound was added at post-inoculation conditions. Without replenishment of the compound, antiviral activity was observed up to roughly five rounds of replication, demonstrating the long-lasting effect of these compounds. Second, as the upper respiratory tract represents the initial site of SARS-CoV-2 replication, we also assessed antiviral activity in air–liquid interface (ALI) cultured human primary bronchial epithelial cells, isolated from healthy volunteers. Resveratrol and pterostilbene showed a strong antiviral effect in these cells up to 48 h post-infection. Collectively, our data indicate that resveratrol and pterostilbene are promising antiviral compounds to inhibit SARS-CoV-2 infection. Because these results represent laboratory findings in cells, we advocate evaluation of these compounds in clinical trials before statements are made whether these drugs are advantageous for COVID-19 treatment.
