MRI Findings and Topographic Distribution of Lesions in Metronidazole-Induced Encephalopathy.

Purpose This study aims to describe the magnetic resonance imaging (MRI) of the brain of five patients diagnosed with metronidazole-induced encephalopathy (MIE). In addition, the aim of our study was to better define the topographic distribution of lesions in MIE. Methods We retrospectively evaluated MRI findings before and after drug cessation in five patients diagnosed with MIE at Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India. The main MRI signal changes and lesion locations were studied. Results Among the patients observed, the average age of the patients with MIE was 55 years (range: 30-70 years). Cerebellar dysfunction, mainly ataxia, and altered mental status were seen in the majority of cases. The most frequently involved sites were the dentate nucleus (cerebellum), brain stem, and corpus callosum (splenium). In diffusion-weighted imaging (DWI), most lesions did not show true restricted diffusion, except for a solitary corpus callosum lesion. Conclusion Although drug-related side effects are more common with long-term use of metronidazole, they may also occur with high doses for short durations. The dentate nucleus, the splenium in the corpus callosum, and the brain stem are the most affected structures. Apart from a solitary lesion of the corpus callosum, all identified lesions were reversible at follow-up MRI after discontinuation of metronidazole. The clinical presentation and characteristic MRI changes are highly specific and can be correlated to make a rapid and more accurate diagnosis of this potentially treatable condition. Prognosis is excellent if detected early.

Identification of Natural Inhibitors Against SARS-CoV-2 Drugable Targets Using Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Approach.

The present study explores the SARS-CoV-2 drugable target inhibition efficacy of phytochemicals from Indian medicinal plants using molecular docking, molecular dynamics (MD) simulation, and MM-PBSA analysis. A total of 130 phytochemicals were screened against SARS-CoV-2 Spike (S)-protein, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). Result of molecular docking showed that Isoquercetin potentially binds with the active site/protein binding site of the Spike, RdRP, and Mpro targets with a docking score of -8.22, -6.86, and -9.73 kcal/mole, respectively. Further, MS 3, 7-Hydroxyaloin B, 10-Hydroxyaloin A, showed -9.57, -7.07, -8.57 kcal/mole docking score against Spike, RdRP, and Mpro targets respectively. The MD simulation was performed to study the favorable confirmation and energetically stable complex formation ability of Isoquercetin and 10-Hydroxyaloin A phytochemicals in Mpro-unbound/ligand bound/standard inhibitor bound system. The parameters such as RMSD, RMSF, Rg, SASA, Hydrogen-bond formation, energy landscape, principal component analysis showed that the lead phytochemicals form stable and energetically stabilized complex with the target protein. Further, MM-PBSA analysis was performed to compare the Gibbs free energy of the Mpro-ligand bound and standard inhibitor bound complexes. The analysis revealed that the His-41, Cys145, Met49, and Leu27 amino acid residues were majorly responsible for the lower free energy of the complex. Drug likeness and physiochemical properties of the test compounds showed satisfactory results. Taken together, the study concludes that that the Isoquercetin and 10-Hydroxyaloin A phytochemical possess significant efficacy to bind SARS-Cov-2 Mpro active site. The study necessitates further in vitro and in vivo experimental validation of these lead phytochemicals to assess their anti-SARS-CoV-2 potential.