An Analysis in Identifying the Mechanism of Action of the Alkaloids Found in Berberis vulgaris on the Treatment and Prevention of SARS-CoV-2

Abstract

Introduction Berberis vulgaris extract is a well-known herbal remedy for treating numerous conditions including coronavirus disease 2019 (COVID-19). The HAB4a method of preparing the extract is a common method used in clinical practice and a further aim of this study was to identify the key alkaloid compounds that are present in an alcohol versus a glycerine-based extraction and determine the mechanism by which these prevent and treat COVID-19. Results and Discussion Identified alkaloid compounds included bervulcine, vulracine, berberrubine, lambertine, berbidine, obamegine, berbamine, berberine, and palmatine in the alcohol-based extract. The glycerine-based extract contained all except bervulcine, vulracine, and berbidine. Berberine and palmatine were the most abundant compounds in both extracts but more berberine was present in the alcohol-based extract and more palmatine in the glycerine-based extraction. Databases revealed compound-gene interactions with human targets involved in signalling and gene regulation networks that could synergistically change cell function. The SARS-CoV-2 spike 1 protein purification yielded about 5 mg of highly purified protein (˃95%) from 1 L of bacterial culture. Isothermal titration calorimetry (ITC) analysis of any potential interaction of palmatine and berberine with the purified spike 1 protein was negative. Thus, it is possible the extract components work in a synergistic manner to prevent and treat COVID-19. Conclusions Berberis vulgaris root extract alkaloid components differ when alcohol or glycerine is used. Berberine and palmatine are the most abundant alkaloids but differ in the amount relative to each other in the extracts. The extract components could affect changes in a variety of human genes. Materials and Methods Ultra-High-Performance Liquid Chromatography—High-Definition quadrupole time-of-flight Mass Spectrometry was used to identify alkaloids. Databases were used to determine the genes that interact with the identified compounds. SARS-CoV-2 spike protein was expressed and purified. Purified protein was used in ITC with berberine and palmatine.