ABSTRACT
Background: Infectious illnesses are a serious health concern in Indonesia. Widespread use of self-medication by the community increases the risk of developing multi-drug resistant (MDR) bacteria. This study assessed the potential of sappan wood as an inhibitor of extended-spectrum beta-lactamase (ESBL) encoded by blaSHV, blaTEM and blaCTX-M genes. Method: In silico testing was conducted to develop an effective and economical starting strategy. Thereby, this study significantly advances the development of novel treatments to combat antibiotic resistance. Using clavulanic acid as the benchmark medicine, the potency of the beta-lactamase inhibitor brazilein was predicted. Using the Molegro Virtual Docker computer tool, docking was performed to estimate the chemical and physical properties of the compounds, as well as the biological activity of brazilein toward the required receptor. The receptors used were SHV-1 beta-lactamase, PDB code: 2H0T; TEM-1 beta-lactamase, PDB code: 4OQG and CTX-M-14 beta-lactamase, PDB code: 6VHS. Data analysis was performed by comparing the binding energies of the docking results between the ligands and the target receptor. The more stable the bond that formed between the ligand and the target receptor, the lower the bond energy. Results: The in silico test results on the blaSHV gene were as follows: binding energy of ligand MA4_400[A] = -100.699, brazilein = -82.206, clavulanic acid = -79.3704; in the blaTEM gene: ligand bond energy 2UL_301[B] = -107.681, brazilein = -82.0296, clavulanic acid = -103.3; in the blaCTX-M gene: X57_301[A] ligand bond energy = -86.6197, and brazilein = -88.1586, clavulanic acid = -101.933. Conclusion: The findings of this study demonstrate the significant potential of brazilein sappan wood to block the beta-lactamase activity of blaCTX-M.
ABSTRACT
Brazilein sappan wood, played by Spike (S) glycoprotein, Papain-Like proteinase (PLpro), and Main protease (Mpro), is expected to be a candidate for the antiviral drug SARS-CoV-2, which can inhibit viral attachment to the human body, replication, and transcription processes. The aim of this study was to predict in silico, using the comparative drug hydroxychloroquine, the working goal of brazilein sappan wood as a candidate for the antiviral drug SARS-CoV-2 against protein S, PLpro, and Mpro. The approach used is the in silico docking test using the computer program Molegro Virtual Docker. Receptor used by protein S, Protein Data Bank (PDB) code: 6M0J, NAG_601[E] ligand; PLpro, PDB code: 7JIT, Y95_501[A] ligand; and Mpro, PDB code: 1WOF, I12_1145[A] ligand. Data analysis was carried out by comparing the docking bond energies between the ligands at the target receptor. Silico test results for protein S: ligand bond energy NAG_601 [E] = -59.4555, brazilein = -71.5537, hydroxychloroquine = -79.3704; PLpro protein: Ligand bond energy Y95_501 [A] = -129.561, brazilein = -94.9761, hydroxychloroquine = -100.984; Mpro protein: Ligand bond energy I12 1145 [A] = -141.135, brazilein = -96.6169, hydroxychloroquine = -104.88. The above test results indicate that brazilein sappan wood has potential as a SARS-CoV-2 drug candidate, has a stable bond, and that the biological activity of the compound is stronger against S protein than the proteins of PLpro and Mpro.
