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DRUG REPURPOSING STRATEGY AS A POTENTIAL THERAPEUTIC DRUG CANDIDATE AGAINST STREPTOCOCCUS SANGUINIS ATCC 10556 BIOFILM
The oral cavity represents the primary interface between the human body and the external environment, where continues exposure of periodontal tissues to ecologically imbalanced polymicrobial dental plaque can lead to periodontal disease. Streptococcus sanguinis acting as a key pioneer colonizer during early oral biofilm formation. The intrinsic resistance of biofilm formation to antibiotics has driven the exploration of alternative therapeutic strategies, including drug repurposing. This study aimed to identify candidate drugs of interest with antibiofilm activity against S. sanguinis biofilm through a combination of MIC assays, biofilm assays, and molecular docking. Based on pharmacovigilance analysis, lamivudine (LAM) was selected as the drug of interest due to its strong association with a reduction reporting of periodontal adverse events (ROR = −2.1290565; Z-score = 96.248094). In vitro showed that LAM significantly inhibited planktonic growth at a lower concentration of 2.5 mg/mL and significant decrease in the number of S. sanguinis ATCC 10556 biofilm bacterial colonies at a concentration of 60 mg/mL with a log10(CFU/cm2). Molecular docking analysis demonstrated that lamivudine binds to the GtfP protein (3AIE) with a lower S score than the native ligand (S score = −4.36) and forms hydrogen bonds with the key residue Tyr978, suggesting a potential inhibitory effect on glucosyltransferase activity. This interaction may disrupt extracellular polysaccharide synthesis and thereby suppress biofilm formation, which is consistent with the reduction in bacterial colony counts observed in the in vitro assays. Keywords: biofilm formation, drug repurposing, lamivudine (LAM), molecular docking, and Streptococcus sanguinis ATCC 10556
FAKULTAS SAINS DAN TEKNOLOGI, UIN SUNAN KALIJAGA YOGYAKARTA
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