Cissampelos pareira (velvetleaf) exhibits anti-SARS-CoV-2 potential

Severe acquired respiratory syndrome agent coronavirus 2 (SARS-CoV-2) has undergone numerous mutations giving rise to more easily transmissible and more infectious variants that can potentially increase disease severity. Yet, no definitive therapy has been developed for COVID-19 so far. Several studies being conducted to recognize small molecules effective against the virus have found some protein synthesis inhibitors and estrogen receptor modulators with potential antiviral activity against SARS-CoV-2.

Some studies have shown that estrogen receptor 1 (ESR1) as a drug target can modulate some genes associated with coronavirus, as estrogen downregulates ACE2.

Since many herbal medicines are sources of various antiviral compounds, accelerated repurposing of antiviral herbs may help identify useful drugs and drug targets against SARS-CoV-2.

Cissampelos pareira (Cipa), also known as velvetleaf, is a widely used hormone modulator used to treat reproductive disorders and fever. Research has shown that it can inhibit three serotypes of Dengue virus (DENV) and affect various hormones.

Study: Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies. Image Credit: Wasanajai / Shutterstock

Exploring the repurposing potential of Cipa for use in the treatment of COVID-19

Recently, Indian researchers dissected the anti-coronavirus activity of Cipa with the help of an integrative approach to explore its repurposing potential for use in this current pandemic.

In a previous study, they observed that Cipa is both a protein synthesis inhibitor and an estrogen receptor inhibitor.

Here, they analyzed the signature similarities between Cipa and predicted antiviral agents using the connectivity map (CMAP) and then tested Cipa’s in vitro anti-SARS-COV-2 activity. They also performed a three-way comparative analysis of COVID-19 bronchoalveolar Lavage fluid (BALF) transcriptome, Cipa transcriptome, and CMAP signatures of small molecules. This study is published on the bioRxiv*preprint server.

“Many of the drugs positively connected with Cipa have been reported to be a potential antiviral agent.”

Findings show that whole plant extract and constituents of Cipa effectively inhibited SARS-COV-2

The results showed that many predicted antivirals such as emetine, apcidin, and homoharringtonine had a high positive connectivity score with Cipa. A 98% inhibition of SARS-COV-2 replication was also observed in infected Vero cell cultures with the whole extract. Some of the prominent pure constituents of Cipa such as pareirarine, magnoflorine, and cissamine exhibited 40-80% inhibition.

On comparing genes of BALF and Cipa, the researchers found that biological processes such as transcription regulation were upregulated by Cipa and downregulated by BALF in COVID-19 patients. CMAP also showed that torin-1, triciribine, and VU-0365114-2 had positive connectivity with BALF 1 and BALF 2, and negative connectivity with Cipa.

Inhibition of SARS-CoV-2 in vitro by Cipa whole extract and its constituents: Relative viral RNA % and Log reduction in viral particles in vero cells upon treatment at 50, 100, 150 and 200μg of A) whole-plant aqueous extract (PE), B) root extract (PER) and C) hydro-alcoholic extracts (PE50) of Cipa. D) Sars-cov-2 viral titers inhibition by Cipa constituents CP-2 Salutaridine, CP-3 Cissamine, CP-5 pareirarine, CP-7 Magnoflorine, PE aqueous extract, PE50 50% hydroalcoholic extract and PER root extract.

Results demonstrate the potential repurposing of Cipa for SARS-COV-2 inhibition using the CMAP approach

This work shows that Cipa with ESR1 modulatory effects and antiviral potential has an inhibitory effect on the novel coronavirus. CMAP analysis of transcriptome signatures of Cipa showed many small compounds with inhibitory activity against SARS-CoV-2. Among these compounds, homoharringtonine, emetine, and cycloheximide are translation inhibitors previously shown to inhibit Zika, Ebola, SARS, the Middle East respiratory syndrome (MERS), and Newcastle disease viruses.

In vitro studies of inhibition of SARS-COV-2 show that aqueous and alcoholic whole plant extracts of Cipa had 60% ability to inhibit the virus, with the hydroalcoholic whole plant extract showing a 98% SARS-COV-2 inhibition.

Cipa’s single-molecule constituents, such as pareirarine, also inhibited the viral particles, proving that Cipa had the potential to inhibit SARS-CoV-2 in vitro.

Since the highest inhibition shown by the hydroalcoholic extract comprises of many small compound constituents, the authors suggest a synergistic effect of the molecules towards viral inhibition.

In conclusion, the authors demonstrate the potential repurposing of Cipa for SARS-COV-2 inhibition using the approach described in this work.

“In summary, we report here a framework applicable for repurposing of herbal formulations using an integrated multi-pronged approach using transcriptome-based connectivity mapping, in vitro validation and conjoint analysis with disease signatures.”

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.