In silico Study Phytosterol Cymbopogon citratus and Curcuma longa as Inhibitor Agent 3C-Like Protease SARS-CoV-2.

<b>Background and Objective:</b> Lemongrass (<i>Cymbopogon citratus</i>) and turmeric (<i>Curcuma longa</i>) are widely used by the community for traditional medicinal spices and cooking spices. In the era of the COVID-19 pandemic, people use lemongrass and turmeric to increase immunity and protect the body from infection with the SARS-CoV-2 virus. However, the antiviral mechanisms have not been studied much. This study aims to predict the bioactivity of the phytosterol compounds of lemongrass and turmeric for COVID-19 therapy through inhibition of 3C-like protease (3CLPro) <i>in silico</i>. <b>Materials and Methods:</b> The 3CLPro protein 3D structure was downloaded from the PDB database with the access code 2ZU2 and the phytosterol compounds of lemongrass and turmeric were taken from PubChem. A total of 59 total phytosterol compounds from turmeric and lemongrass were screened for their bioactivity as an antiviral by using online PASS. Compounds with a high activating potential (Pa) were interacted with 3CLPro protein with the PyRx program and analyzed by Discovery Studio version 19.0 and LigPlus. <b>Results:</b> A total of 22 total phytosterol compounds were identified as potential antiviral agents. Based on the Pa value, 15 phytosterol compounds have the potential to act as inhibitor agents for 3CLPro SARS-CoV-2. The phytosterol compounds of lemongrass and turmeric bind to the 3CLPro protein in the N-finger domain region and the A and B domain inhibitors connect residues of the 3CLPro protein. The phytosterols of lemongrass and turmeric show a low binding affinity with 3CLPro SARS-CoV-2, indicating a strong interaction between ligand and protein. The inhibition of phytosterols against 3CLPro protein can be used as a basis for determining candidates for COVID-19 therapeutic agents. <b>Conclusion:</b> The phytosterol compounds contained in lemongrass and turmeric have the potential to act as 3CLPro inhibitors. Further studies both <i>in vitro</i> and <i>in vivo</i> need to be done to prove the inhibitory potential of phytosterol compounds.

Gamma-oryzanol as an example of a complex of phytosterol esters and ferulic acid with broad biological activity / Gamma-oryzanol jako przyklad kompleksu estrów fitosteroli i kwasu ferulowego o szerokiej aktywnosci biologicznej.

Plants are natural laboratories producing a cornucopia of secondary metabolites of huge therapeutic potential. The oil extracted from rice bran, a by-product of brown rice processing, is abundant in valuable bioactive substances. One of its main ingredients is gamma-oryzanol that is a mixture of phytosterol esters and ferulic acid. These compounds exert a wide range of biological activities closely correlated with their chemical properties. Their hypocholesterolemic and antioxidant abilities are crucial for improving the physiology and condition of the human body. For these reasons, there has been a clear increase in the number of studies investigating the use of gamma-oryzanol in the treatment of many chronic diseases, and it is even tested as a promising non-pharmacological therapeutic agent in the treatment of COVID-19 in overweight people. This paper describes the chemical structure and activity of gamma-oryzanol based on biological activity of phytosterol esters and ferulic acid. It also discusses the effects of gamma-oryzanol on some physiological processes in the human and animal organisms.

Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (Mpro).

The current research used a virtual screening method to study 57 isolated phytochemicals (alkaloids, phytosterols, and flavonoids) against the SARS-CoV-2 main protease (Mpro). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the selected compounds were analysed using admetSAR tool while SwissADME and Molinspiration chemoinformatics tools were used to examine the oral bioavailability and drug-likeness properties. Parameters such as physicochemical properties, activity spectra for substances (PASS) prediction, bioactivity, binding mode, and molecular interactions were also analysed. Our results favoured Lupeol (-8.6 kcal/mol), Lupenone (-7.7 kcal/mol), Hesperetin (-7.4 kcal/mol), Apigenin (-7.3 kcal/mol) and Castasterone (-7.3 kcal/mol) as probable inhibitors of SARS-CoV-2. This is because of their good binding affinities, bioactivities, drug-likeness, ADMET properties, PASS properties, oral bioavailability, binding mode and their interactions with the active site of the target receptor compared to Remdesivir and Azithromycin. Therefore, these compounds could be explored towards the development of new therapeutic agents against SARS-CoV-2.