Delineating a potent antiviral activity of Cuphea ignea extract loaded nano-formulation against SARS-CoV-2: In silico and in vitro studies

Abstract

Journal of Drug Delivery Science and Technology Available online 15 September 2021, 102845 In Press, Journal Pre-proofWhat are Journal Pre-proof articles? Delineating a potent antiviral activity of Cuphea ignea extract loaded nano-formulation against SARS-CoV-2: In silico and in vitro studies Author links open overlay panelDina B.MahmoudaWalaa M.IsmailbYassminMoatasimcOmniaKutkatcAliaa N.ElMeshaddeShahira M.EzzatbfKadriya S.El DeebbAhlam M.El-FishawybMokhtar R.GomaacAhmedKandeilcAhmed A.Al-karmalawygMohamed A.AlicAhmedMostafac a Pharmaceutics Department, National Organization for Drug Control and Research, Giza, Egypt b Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr-El-Ainy Street, Cairo, 11562, Egypt c Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt d Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr-El-Ainy Street, Cairo, 11562, Egypt e Faculty of Nanotechnology for Postgraduate Studies, Cairo University, El Sheikh Zayed, Giza, 12588, Egypt f Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, 12451, Egypt g Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta, 34518, Egypt Received 7 March 2021, Revised 17 July 2021, Accepted 5 September 2021, Available online 15 September 2021.

https://doi.org/10.1016/j.jddst.2021.102845 Get rights and content Abstract The outbreak of coronavirus disease-2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a worldwide emerging crisis. Polyphenols are a class of herbal metabolites with a broad-spectrum antiviral activity. However, most polyphenols encounter limited efficacy due to their poor solubility and degradation in neutral and basic environments. Thus, the effectiveness of their pharmaceutical application is critically dependent on the delivery systems to overcome the aforementioned drawbacks. Herein, Polyphenols-rich Cuphea ignea extract was prepared and its constituents were identified and quantified. Molecular docking was conducted for 15 compounds in the extract against SARS-CoV-2 main protease, among which rutin, myricetin-3-O-rhamnoside and rosmarinic acid depicted the most promising antiviral activity. Further, a self-nanoemulsifying formulation, composed of 10% oleic acid, 40% tween 20 and propylene glycol 50%, were prepared to improve the solubility of the extract components and enable its concurrent delivery permitting combined potency. Upon dilution with aqueous phases, the formulation rapidly form nanoemulsion of good stability and excellent dissolution profile in acidic pH when compared to the crude extract. It inhibited SARS-CoV-2 completely in vitro at a concentration as low as 5.87 μg/mL presenting a promising antiviral remedy for SARS-CoV-2, which may be attributed to the possible synergism between the extract components.