Flavonoids of Salvadora persica L. (meswak) and its liposomal formulation as a potential inhibitor of SARS-CoV-2

Abstract

Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant extract and its liposomal formulation were shown to inhibit SARS-CoV-2 in an in vitro A549 cell line culture and a RT-PCR test almost as well as the FDA-approved anti-COVID-19 agent, remdesivir. Encapsulation within liposomal formulation led to a highly significant increase in the percentage of inhibition of viral replication from 38.09 ± 0.83 to 85.56 ± 1.12% in a flavonoid mixture and its liposomal preparation, respectively, and this figure approached that obtained for remdesivir (91.20 ± 1.71%). Preliminary tests were also performed, including a total flavonoid assay, a molecular docking study, a 3CL-protease inhibition assay and a cytotoxicity study. It was worthy to find a cheap, readily available, safe natural source for promising anti-SARS-CoV-2 agents, that leak their phytochemicals into the aqueous saliva during regular use as a brushing agent.

Fig. 1. Chemical structures of the major compounds present in FRF.

Fig. 2. The alpha sphere (A) of the main binding pocket between hACE2 (B) and the COVID-19 spike protein (C).

Fig. 3. A 3D representation of the docking poses of compound 2 on the COVID-19 spike binding site with hACE-2.

Fig. 4. A 2D representation of the docking of compound 2 on the COVID-19 spike binding site with hACE-2.

Fig. 5. The TEM image and the particle size distribution of FRF-Lip.