Introduction: Uncontrolled biofilm can cause several diseases such as dental caries, gingivitis, and periodontitis. Dental caries is a disease caused by the accumulation of plaque-containing pathogenic bacteria, including Enterococcus faecalis. These bacteria infect the root canals of teeth and colonize to form biofilms. Biofilm inhibition is carried out by interfering with cell wall formation metabolism. MurA enzyme has a role in peptidoglycan biosynthesis of cell walls. Enterococcal surface protein (Esp) is the main contributor of E. faecalis to form biofilms. In addition, inhibition of biofilms by interfering with the quorum sensing (QS) system, suppressing gelatinase virulence factors by blocking autoinducers gelatinase biosynthesis-activating pheromone (GBAP). Purpose: Knowing the potential of Piper betel Linn. compounds as antibacterial in vitro and antibiofilm agents against E. faecalis in silico. Patients and Methods:The compounds were purified by a bioactivity-guided chromatographic method. Antibacterial activity was tested by disc diffusion method, in vitro studies. In silico study, compound P. betel L. was used as the test ligand and compared with positive control fosfomycin, ambuic acid, quercetin, and taxifolin. The proteins used MurA, Esp, GBAP, and gelatinase were docking with the Autodock Vina PyRx 0.8 followed by the PYMOL program and visualized with the Discovery Studio 2020 program. Results: An antibacterial compound was identified 24-propylcholesterol which can inhibit the activity of E. faecalis ATCC 29212 with MIC value of 78.1 µg/mL and MBC value of 156.3 µg/mL. Molecular docking results showed the binding affinity of 24-propylcholesterol with MurA, ESP, GBAP, and gelatinase enzymes was −7.6, −8.7, −5.3, and −7.9 kcal/mol. Conclusion: 24-propylcholesterol has potential as an antibacterial against E. faecalis and as an antibiofilm through in silico inhibition of QS. However, further research is needed in vitro and in vivo to determine the effectiveness of these compounds as antibacterial and antibiofilm.
Background: COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has infected millions of people and caused hundreds of thousands of deaths worldwide. However, until now there has not been found a specific drug for SARS-CoV-2 infection. This prompted many researchers to explore compounds as anti-SARS-CoV-2 candidates. One of the efforts to deal with the spread of the COVID-19 virus is to increase the body's immune system (immune). Medicinal plants known to have the ability as immune-modulators, one of which is Betel leaf (Piper betle L.) those reported to have good activity as antibacterial, antioxidant, anti-viral, and other pharmacological effects. An in silico approach in drug development was used to search for potential antiviral compounds as inhibitors of SARS-CoV-2 Mpro Protein, RBD, and Non-structural Protein (NSP15). Objective:: This study was to determine the potential of Betel leaf compounds as immune-modulators and good inhibitory pathways against COVID-19. Methods: In this study, a potential screening of steroid class compounds, namely 24-propilcholesterol was carried out as an anti-SARS-CoV-2 candidate, using an in silico approach with molecular docking simulations for three receptors that play an important role in COVID-19, namely Mpro SARS-CoV-2, RBD SARS-CoV-2 and non-structural protein (NSP15) and compared with Azithromycin, Favipiravir and Ritonavir as positive control. Results: Based on the results of molecular docking simulations compound from Betel leaf, 24-Propylcholesterol, showed high binding affinity values for spike glycoprotein RBD and non-structural protein 15 (NSP15), namely -7.5 and -7.8 kcal/mol. Meanwhile, a native ligand of Mpro, inhibitor N3, has a higher binding affinity value than 24-propylcholesterol -7.4 kcal/mol. Conclusion: 24-Propylcholesterol compound predicted to have potential as an anti-SARS-CoV-2 compound. However, it is necessary to carry out in vitro and in vivo studies to determine the effectiveness of the compound as an anti-SARS-CoV-2
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