Anti-SARS-CoV-2 in vitro potential of castor oil plant (Ricinus communis) leaf extract: in-silico virtual evidence.

Ricinus communis L. is a medicinal plant that displays valuable pharmacological properties, including antioxidant, antimicrobial, analgesic, antibacterial, antiviral and anti-inflammatory properties. This study targeted to isolate and identify some constituents of R. communis leaves using ultra-performance liquid chromatography coupled with mass spectroscopy (UPLC-MS/MS) and different chromatographic techniques. In vitro anti-MERS and anti-SARS-CoV-2 activity for different fractions and for two pure isolated compounds, lupeol (RS) and ricinine (RS1) were evaluated using a plaque reduction assay with three different mechanisms and IC50 based on their cytotoxic concentration (CC50) from an MTT assay using Vero E6 cell line. Isolated phytoconstituents and remdesivir are assessed for in-silico anti-COVID-19 activity using molecular docking tools. The methylene chloride extract showed pronounced virucidal activity against SARS-CoV-2 (IC50 = 1.76 µg/ml). It was also shown that ricinine had superior potential activity against SARS-CoV-2, (IC50 = 2.5 µg/ml). Lupeol displayed the most potency against MERS, (IC50 = 5.28 µg/ml). Ricinine appeared to be the most biologically active compound. The study showed that R. communis and its isolated compounds have potential natural virucidal activity against SARS-COV-2; however, additional exploration is necessary and study for their in vivo activity.

Antiviral activity of castor oil plant (Ricinus communis) leaf extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Ricinus communis L., commonly known as castor oil plant, is a precious traditional medicine with a history of thousands of years in the world. Castor oil plant has high traditional and medicinal values for treating liver infections, stomach ache, flatulence, constipation, inflammation, warts, colic, enteritis, fever, headache, and as a counter irritant. Its diverse phytochemicals have a wide range of valuable medicinal activities including hepatoprotective, anti-nociceptive, antioxidant, antiulcer, anticancer, anti-inflammatory, central analgesic, antidiabetic, antimicrobial, antiviral, and wound healing activity. AIM OF THE WORK: To provide a complete characterization of the composition of Ricinus communis leaves using ultra-performance liquid chromatography coupled with hybrid triple time-of-flight mass spectrometry (UPLC-Triple TOF-MS/MS) and different chromatographic techniques and to evaluate its antiviral potential using three mechanisms against three common viruses. MATERIALS AND METHODS: R. communis leaves were extracted with 70% methanol and further partitioned with solvents of increasing polarities: petroleum ether, dichloromethane (CH2Cl2), ethyl acetate, and n-butanol. The CH2Cl2 and n-butanol fractions were subjected to repeated chromatographic separation to isolate the phytochemicals, and their structures were elucidated using nuclear magnetic resonance spectroscopy. UPLC-Triple TOF-MS/MS was performed to determine the different phytochemicals in the ethyl acetate fraction. The antiviral activity of the extracts was investigated using the maximum nontoxic concentration of each against the challenge dose of the virus (CDV) and 1/10 and 1/100 dilutions of the CDV for Coxsackie B virus type 4 (COXB4), herpes simplex virus type 1 (HSV1), and hepatitis A virus (HAV) using Vero cell cultures that were treated according to three protocols to test for anti-replicative, protective, and anti-infective antiviral activity. Cell viability was evaluated using the MTT colorimetric assay and each experiment is repeated three times independently of each other. RESULTS: R. communis leaves possessed antiviral activity. Evaluation of the anti-replicative activity showed that all extracts possessed high anti-replicative activity against HAV especially methanol and methylene chloride fractions and moderate activity against COXB4; butanol > methylene chloride and ethyl acetate > methanol. All extracts showed protective activity against HAV, especially butanol extract, while methanol extracts showed higher non-significant antiviral protective activity against HSV1 vs Acyclovir. Almost no anti-infective effects were recorded for any extract against the studied viruses. CONCLUSION: The discriminatory effect against each virus by different mechanisms suggests the presence of different chemical compounds. The alkaloid and phenolic derivatives of the extracts of R. communis leaves may help develop a drug to prevent or treat common viral infections. Further investigations are recommended to define the bioactive antiviral properties of R. communis leaves.