Anti-SARS-CoV-2 in vitro potential of Castor Oil Plant (Ricinus communis) Leaf Extract: In-Silico Virtual Evidence

Abstract

Abstract Background Ricinus communis L. is a medicinal plant displays valuable pharmacological properties. Diverse phytochemical constituents display valuable pharmacological properties, including antioxidant, antimicrobial, analgesic, antipyretic, antibacterial, antiviral, and anti-inflammatory property. 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, then characterize the potential cytotoxicity, anti-MERS-CoV and anti-SARS-CoV-2 activity in vitro. Isolated phytoconstituents and remdesivir are assessed for in-silico anti-COVID-19 activity by inhibiting the main protease and spike protein using molecular docking tools. Methods: The CH2Cl2 fraction was 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 CH2Cl2 fraction. The in vitro anti-MERS and anti-SARS-CoV2 activity for different fractions and for two pure isolated compounds, lupeol (RS) and ricinine (RS1) were evaluated using Plaque reduction assay and IC50 based on their cytotoxic concentration (CC50) from an MTT assay using Vero E6 cell line. Molecular docking studies were carried out for both SARS-CoV-2 spike (S) and main protease (Mpro) receptors then examined the possible mechanisms of action. Results: The methylene chloride extract exhibited pronounced virucidal effect with more than a 90% viral inhibitory effect, it showed activity against SARS-CoV- 2 (IC50 = 1.76µg/ml) with high safety index, SI = 291.5. It was also shown that ricinine had superior potential activity against SARS-CoV-2, (IC50 = 2.5 µg/ ml). This constituent was less effective for MERS, IC50 = 87.2 µg/ ml. Lupeol displayed the most potency against MERS, (IC50 = 5.28 µg/ ml), SI = 67.27, but was less effective for SARS, IC50 = 19.5 µg/ ml. Ricinine showed significant binding to (3CLpro) and modest affinity for (S) spike protein, along with a possible interaction with SARS-CoV-2 major protease. Ricinine appeared to be the most biologically active. Conclusion: The study showed that Ricinus communis and its isolated compounds have potential natural virucidal activity against SARS-COV-2, however, additional exploration is necessary for further chemical modification of these structures, guided by the molecular docking tools and study for their in vivo activity.