IN-SILICOIDENTIFICATION OF FLAVONOIDS BASED INHIBITORS AGAINST SORTASE-A FROM ENTEROCOCCUS FAECALIS (Ef)

The enzyme known as SortaseA(SrtA) is widespread present in gram-positive bacteria. SrtA is responsible for anchoring a large number of surface protein virulence factors to the cell wall. This enzyme is not involved in bacterial growth and is also present on the cell membrane, which makes it more accessible for the design of inhibitors. In the case of Enterococcus faecalis (Ef), which is responsible for a wide range of nosocomial infections, SrtA from this organism promotes development of biofilm, which in turn makes bacteria resistant to antibiotics. Numerous inhibitors have been identified and characterized against Ef-SrtA; however, none have been clinically approved till now. Natural compounds and their derivatives showed inhibition against Ef-SrtA. In this work, a flavanoids-based in-house natural library was screened against Ef-SrtA to see how these molecules bind to active site of Ef-SrtA. Furthermore, the absorption, distribution, metabolism and excretion (ADME) properties of the top five compounds, Abyssinones lii, Apigenin, Rutin, Fisetin and Kaemferol, were calculated, Additionally, the correlation between the structure and function of these top five compounds was analyzed using Density Functional Theory (DFT) studies.