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A team of scientists from the University of Groningen, in the Netherlands, shows that a natural plant product, resveratrol, and its structural analog, pterostilbene, have long-lasting antiviral effects against severe acute respiratory infection caused by coronavirus 2 (SARS-CoV). -two). . The study is currently available at bioRxiv* prepress server.
Since its emergence in late December 2019 in China, SARS-CoV-2, the pathogen that causes coronavirus disease 2019 (COVID-19), has shown an unstoppable transmission trajectory around the world. Although continuous efforts are being made in the search for effective therapies or vaccines, there is still a long way to go before finding a solution to contain the COVID-19 pandemic.
The severe form of COVID-19 is known to be associated with severe lung inflammation induced by both viral infection and host antiviral immune responses. Several phytochemicals with anti-inflammatory and antioxidant properties, such as resveratrol, have been shown to have potent antiviral effects against a wide variety of pathogens, including the Middle East respiratory syndrome coronavirus (MERS-CoV), the human immunodeficiency virus (HIV ), influenza virus and respiratory syncytium virus. In terms of mode of action, resveratrol has been shown to directly inhibit the viral replication cycle.
Given the potential antiviral properties of resveratrol, the current study has been conducted to evaluate the effect of resveratrol and its structural analog, pterostilbene, in the treatment of SARS-CoV-2 infection.
Antiviral effect of resveratrol and pterostilbene against SARS-CoV-2 in Vero E6 cells. Production of infectious virus by Vero E6 cells inoculated with SARS-CoV-2 in MOI 1 in the absence (NT denotes untreated) or presence of increasing concentrations of (a) resveratrol, (b) pterostilbene, or the EtOH solvent control. (c) EC50 and EC90 values determined by nonlinear regression analysis. (d, e) Durability of the antiviral effect of (d) resveratrol and (e) pterostilbene at 16, 24, 40 and 60 hours after inoculation (hpi). The dotted line indicates the detection threshold. Data are represented as mean ± SEM of at least three independent experiments. Each symbol represents data from a single independent experiment. The Student’s t test was used to evaluate statistical differences and a value of p ≤ 0.05 with * p ≤ 0.05, ** p ≤ 0.01 and *** p ≤ 0.001 was considered significant. In the absence of ‘*’, the data is not significant.
Current study design
The scientists used different types of cells, including monkey kidney cells, human lung epithelial cells, and human primary bronchial epithelial cells, to investigate whether resveratrol and pterostilbene can inhibit the replication of SARS-CoV-2. in vitro.
Important remarks
Scientists initially determined the dose-dependent cytotoxicity of resveratrol and pterostilbene. Based on these findings, they decided to use 150 µM resveratrol and 60 µM pterostilbene as the highest experimental doses to continue with all subsequent experiments.
To induce infection, monkey kidney cells were inoculated with SARS-CoV-2 and treated simultaneously with resveratrol and pterostilbene. They observed that both resveratrol and pterostilbene reduced the production of the viral particle in a dose-dependent manner. Compared to resveratrol, pterostilbene was found to be a more potent antiviral agent, reducing viral progeny even at lower doses. Furthermore, both compounds showed strong antiviral effects over a prolonged period of time.
To determine the mode of action of resveratrol and pterostilbene, they performed a drug addition time experiment in which they administered the compounds before, during, and after viral inoculation. In general, no effect on the production of viral particles was observed when the compounds were added before creating the infection. A slight effect was observed when the compounds were added during infection. Interestingly, a significant reduction in the production of viral particles was observed when the compounds were added after creating the infection. Furthermore, no effect was observed when the compounds were added at a time representing viral assembly and virion release. These observations indicate that the antiviral effects of both resveratrol and pterostilbene are most prominent at a time between viral entry and virion release, meaning that the compounds act primarily by inhibiting the viral replication cycle.
Although both resveratrol and pterostilbene did not show any significant antiviral effect on human lung epithelial cells, a potent and long-lasting antiviral effect of resveratrol and pterostilbene against SARS-CoV-2 infection was observed in fully human primary bronchial epithelial cells. differentiated.
Important things to remember
Based on the study findings, both resveratrol and pterostilbene have the potential to be used as antiviral agents against SARS-CoV-2. However, one crucial thing to consider is that the study has been conducted using in vitro models, and therefore does not indicate that these compounds are actually effective in treating COVID-19 patients. Therefore, these compounds should not be consumed as preventive or curative medications until an affirmative response from appropriate human clinical trials has been obtained.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.
