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.

Footwear Affects Biomechanical Work And Knee Adduction Moment During Stance Phase In Medial Knee Osteoarthritic Male Pakistani Adults.

OBJECTIVE: The objective of this study was to explore the effects of commonly used footwear in urban Pakistan on knee adduction moment (KAM), knee adduction angular impulse (KAAI) and biomechanical work at lower limb joints (both individually and collectively). METHODOLOGY: Cinematographic gait analysis of 20 medial knee osteoarthritis patients (Kellgren-Lawrence Grade I and II, age: 55.48 ± 5.78 years; weight: 68.92 ± 9.61 kg, height: 1.62 ± 0.15m) was done, walking barefoot, with casual shoes, party shoes and traditional Pakistani sandals, at a walking speed of 1.2m/sec. RESULTS: Repeated measures ANOVA with Tukey corrections showed that all the shoes were found to be increasing first & second peaks external KAM and decreasing net joint work and total limb work significantly, at p < 0.05. CONCLUSION: Effects of footwear were found to be majorly favouring knee osteoarthritis progression. This might be one of the risk factors of increased kOA rate in urban Pakistan.