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.
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. 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.
ABSTRACT
In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) commenced in Wuhan, China and affected around 210 countries and territories in a matter of weeks. It has a phylogenetic similarity to SARS-CoV and it was named coronavirus 2 (SARS-CoV-2) and caused severe acute respiratory syndrome that could lead to death. One of the promising therapeutic strategies for virus infection is the search for enzyme inhibitors among natural compounds using molecular docking in order to obtain products with minimal side effects. COVID-19 virus main protease plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target. Metabolic profiling of the aqueous extract of Salvadora persica L. (Salvadoraceae) aerial parts dereplicated eleven known flavonol glycosides using LC-HRESIMS. All the annotated flavonoids exhibited significant binding stability at the N3 binding site to different degrees, except isorhamnetin-3-O-ß-d-glucopyranoside, when compared with the currently used COVID-19 main protease inhibitor, darunavir. Structural similarity between the identified flavonoids enabled the study of the relationship between their structure and interactions with the receptor in the N3 binding site of the COVID-19 main protease. The results indicate that the basic flavonol nucleus possesses activity itself. Moreover, the presence of a rutinose moiety at the 3 position of ring C and absence of an O-methyl group in ring B of the flavonol structure could increase the binding stability. This study provides a scientific basis for the health benefits of the regular use of S. persica as it leaches bioactive flavonoids in the aqueous saliva.