A team of scientists from India has recently studied the antiviral potential of a traditional medicinal plant. Cissampelos pareira L. in the prevention of acute coronavirus 2 (SARS-CoV-2) respiratory syndrome infection. The findings indicate that both whole plant extracts and bioactive fertilizers can inhibit SARS-CoV-2 reproduction by altering estrogen receptor 1 (ESR1) activity. The study is currently available on the bioRxiv* preprint server.
Background
Since its outbreak in late December 2019 in Wuhan, China, SARS-CoV-2, the causative pathogen of coronavirus 2019 (COVID-19), has captured more than 111 million people and 2.46 million lives across the globe.
In an effort to block the COVID-19 pathway, several vaccines that may target the viral spike protein have been developed at a faster pace. Some of these vaccines have already been licensed for emergency use in many countries. In addition, a large number of human clinical trials have been conducted to determine the effectiveness of reconstituted antiviral drugs, monoclonal therapeutic antibodies, and small molecular protectors in the treatment of COVID- patients. 19 moderate to severe. In addition to pharmacological interventions, the anti-SARS-CoV-2 efficacy of many other medications, such as phytochemicals, has been extensively studied to develop cost-effective COVID-19 therapeutic treatment with sub- minimum effects.
Cissampelos pareira L. (Cipa) is one such medicinal plant that is traditionally used to treat hormonal imbalance, fever, cough, skin ulcer, jaundice and asthma. There is evidence to suggest that aqueous and ethanolic extracts of Cipa have antiviral and antimalarial properties. In the present study, the scientists have described genome-wide expressions of human breast cancer cell lines treated with Cipa to evaluate the mode of action and antiviral strength of Cipa.
Study design
In particular, the scientists treated the cells with different concentrations of whole plant aqueous / ethanolic extracts of Cipa and isolated RNA samples to perform a complete transcriptional analysis. Next, they performed a Gene Set Wealth Study to identify specific sets of Cipa-modulated genes. By analyzing the different expression counts of genes, they aimed to determine the involvement of Cipa in different cell pathways, as well as to study its connection to process-capable substances. intracellular alteration.
Plot for virtual dock sites of 61 Cipa MPs (four groups, pink, green, orange and blue) and tamoxifen binding site (pink) and 17 beta estradiol (blue) on alpha receptor.
Important comments
Using gene ontology analysis, the scientists found that Cipa treatment reduced a specific set of genes involved in lipid metabolism pathways. Similarly, by performing a Gene Set Wealth Analysis, they found that the treatment of Cipa caused both upregulation and downregulation of specific genes involved in the estrogen signaling pathway. In particular, they observed a decrease in mRNA expression of estrogen receptor 1 (ESR1), which they further confirmed by real-time quantitative analysis. To obtain information on potential binding sites, they conducted a meaningful screening of bioactive compounds present in Cipa against ESR1 and identified 4 favorable binding sites for a total of 61 compounds.
In addition, they performed a linkage map analysis using the database obtained from genome-wide transcriptional analysis and observed a high binding score between Cipa and protein synthesis inhibitors (emetine, cycloheximide, verrucarin -a, and cephaeline) which are known to have antiviral activities. in vitro. Upon further analysis, they found that the treatment of Cipa significantly reduced the mRNA expression of ribosomal protein L7 (RPL7), which is a synergist of ESR1.
To investigate whether the antimicrobial activities of Cipa are altered through ESR1, they gave Cipa to two cell lines with Dengue virus expressing ESR1 differently. The results showed that Cipa-mediated inhibition of the Dengue virus was higher in cells expressing a high level of ESR1. Furthermore, they found that the inhibitory effect of Cipa virus was reduced by the depletion of ESR1 in these cells.
To investigate the association between Cipa and SARS-CoV-2, they analyzed transcription data of COVID-19 patients and observed high expression levels of both ESR1 and RPL7. With these observations, they examined the efficacy of Cipa in altering SARS-CoV-2 infection. Using cells with SARS-CoV-2 infection, they found that both aqueous and ethanolic extracts of Cipa caused a significant reduction in viral RNA levels, demonstrating the strong antiviral efficacy of Cipa against the virus. Upon further analysis, they found that specific bioactive fertilizers present in Cipa extracts could also significantly reduce RNA levels of SARS-CoV-2 in infectious cells.
Investigate meaning
The study highlights the potential antiviral efficacy of Cipa extracts, which are traditionally used as a potent balancing hormone of Ayurvedic drugs. The findings indicate that Cipa activates actions against SARS-CoV-2 by altering the estrogen signaling pathway. In addition, the study clarifies that estrogen receptors may be potential therapeutic targets against COVID-19.
* Important message
bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.