Resveratrol and Pterostilbene Inhibit SARS-CoV-2 Replication in Air–Liquid Interface Cultured Human Primary Bronchial Epithelial Cells

Abstract

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.

Protective Role of Combined Polyphenols and Micronutrients against Influenza A Virus and SARS-CoV-2 Infection In Vitro

“…Besides their established antioxidant and anti-inflammatory properties, several studies demonstrated their significant protection against viruses and several pathogens, including the Epstein–Barr and herpes simplex viruses [ 5 , 6 , 7 ]. We have already demonstrated the ability of resveratrol in inhibiting the replication of influenza A virus [ 8 ], and recent research in this field demonstrates that various types of polyphenols, such as resveratrol and pterostilbene, are promising antiviral compounds to inhibit SARS-CoV-2 infection [ 9 ]; indeed, other research aligns perfectly with these results [ 10 , 11 ].…”

Construction, Characterization and Application of Recombinant Porcine Deltacoronavirus Expressing Nanoluciferase

“…To investigate the feasibility of the Nluc reporter viruses for antivirals screening, we selected two drugs that were reported to have a negative effect on CoVs replication, namely lycorine [ 43 ] and resveratrol [ 44 ]. To exclude cytotoxic side effects, cell viability upon lycorine treatment was determined.…”

“…Compared to previously reported real-time cell analysis (RTCA) systems for high-throughput screening of antivirals [ 50 ], the Nluc reporter virus possesses the obvious advantages with more simpler operation features. A recent study showed that resveratrol inhibits SARS-CoV-2 infection in Vero E6 cells and air–liquid interface cultured human primary bronchial epithelial cells (PBEC) as opposed to human lung epithelial cells (Calu-3), suggesting inherent differences between these different cell line models [ 44 ]. However, PDCoV possesses unusual wide cell tropisms.…”

In Vitro and In Silico Interaction Studies with Red Wine Polyphenols against Different Proteins from Human Serum

“…The results revealed that resveratrol targeted caspase 3 in Vero E6 cells, as well as the nucleocapsid protein of MERS CoV. A concentration ranging from 31.5 to 125 µM and 0.5 mg/mL (2.05 mM) was shown to have a positive effect against MERS-CoV and SARS-CoV, respectively, in Vero E6 cells [63,64]. Moreover, it reduced the viral RNA levels and infectious titers.…”