Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

Effects of task-oriented training on dexterous movements of hands in post stroke patients.

Objective: The objective of the study was to determine the effect of task-oriented training on the dexterous movements of hands in Hemiplegic post-stroke patients.Methods: This study has been registered on site ClinicalTrial.gov with clinical trial number NCT05201196. The study was Randomized controlled trial, 18 patients were recruited that meet the inclusion criteria, randomly allocated to task-oriented training Group A (n = 9) and Conventional Therapy Group B (n = 9). Both exercise trainings were applied for 45 min/session, 5 times/week for 6 weeks. Fugl-Meyer Assessment Scale Motor, sensory and coordination portion, Wolf Motor Function Scale and Barthel Index were used as outcome measures, assessed patients at Baseline, after 3 weeks and 6 weeks after training. Data were analyzed by SPSS version 23.Results: The results suggested the mean Age was 60.78 ± 9.08 and 61.33 ± 6.78 for Group A and Group B, respectively. Average BMI was 23.66 ± 2.66 for Task-oriented group and 21.36 ± 2.46 for Conventional group. Fugl-Meyer scale shows significant P-value 0.03 post treatment compare to pre-treatment which was .283, Wolf Motor Function test and Barthel Index also showed significant P-values as 0.023 and 0.007, respectively, indicating that Task-oriented training shows more significant improvements than conventional group.Conclusion: Task-based training produced statistically significant as well as clinically meaningful enhancement in the dexterous hand movements of acute and subacute stroke patients than conventional therapy and ultimately improves the functional independence in their daily activities such as feeding, bathing and hygiene.