MATERIALS AND METHODS: Thirty single-rooted mandibular premolars were standardized and prepared using ProTaper rotary files. The specimens were divided into a control group and two experimental groups receiving Diapex and Odontopaste medicament, either filled with iRoot SP or OrthoMTA, for 1 week. Each root was sectioned transversally, and the push-out bond strength and failure modes were evaluated. The data were analyzed using Kruskal Wallis and Mann-Whitney U post hoc test.
RESULTS: There was no significant difference between the bond strength of iRoot SP and OrthoMTA without medicaments and with the prior placement of Diapex (p value > 0.05). However, iRoot SP showed significantly higher bond strength with the prior placement of Odontopaste (p value < 0.05). Also, there was no association between bond strength of OrthoMTA with or without intracanal medicament (p value > 0.05) and between failure mode and root filling materials (p value > 0.05). The prominent failure mode for all groups was cohesive.
CONCLUSION: Prior application of Diapex has no effect on the bond strength of iRoot SP and OrthoMTA. However, Odontopaste improved the bond strength of iRoot SP.
CLINICAL SIGNIFICANCE: Dislodgment resistance of root canal filling from root dentin could be an indicator of the durability and prognosis of endodontic treated teeth.
OBJECTIVE: Aim of the present study was to analyse the molecular interaction of nitrogen heterocyclic based drugs (hydroxychloroquine, remdesivir and lomefloxacin) with various SARSCoV- 2 proteins (RdRp, PLPro, Mpro and spike proteins) using a molecular docking approach.
METHODS: We have performed docking study using PyRx software, and Discovery Studio Visualizer was used to visualise the molecular interactions. The designed nitrogen heterocyclic analogues were checked for Lipinski's rule of five, Veber's Law and Adsorption, Distribution, Metabolism, and Excretion (ADME) threshold. After obtaining the docking results of existing nitrogen heterocyclic drugs, we modified the selected drugs to get molecules with better affinity against SARS-CoV-2.
RESULTS: Hydroxychloroquine bound to RdRp, spike protein, PLPro and Mpro at -5.2, -5.1, -6.7 and -6.0 kcal/mol, while remdesivir bound to RdRp, spike protein, PLPro, and Mpro at -6.1, -6.9, -6.4 and -6.9 kcal/mol, respectively. Lomefloxacin bound to RdRp, spike protein, PLPro and Pro at -6.4, -6.6, -7.2 and -6.9 kcal/mol. ADME studies of all these compounds indicated lipophilicity and high gastro intestine absorbability. The modified drug structures possess better binding efficacy towards at least one target than their parent compounds.
CONCLUSION: The outcome reveals that the designed nitrogen heterocyclics could contribute to developing the potent inhibitory drug SARS-CoV-2 with strong multi-targeted inhibition ability and reactivity.