Prospective Hybrid Molecules with Dual Anti-Viral and Anti-Thrombotic Activity Against the SARS-CoV-2 Infection and Its Associated Complications Employing in Silico Studies

Covid-19, a SARS-CoV virus-based disease, was identified in Wuhan, China, in December 2019. Initially, it was considered just an infection of the respiratory system, but due to its transmittable nature, it was declared a pandemic. A variety of treatment options were implemented, including antivirals like remdesvir, favipiravir along with vitamins and antioxidants. Further investigations revealed that the Covid-19 infection results in thrombotic cardiovascular complications, which are the major concern for the increased mortality associated with this disease. This study investigates the in Silico design of hybrid molecules with antiviral and an-tithrombotic properties. A docking study was performed using Autodock Vina software, and binding energies of the designed compounds were determined for papain-like protease (PDB: 3E9S) and 3-chymotrypsin-like cysteine protease (PDB: 6LU7). The docked poses and amino acids interactions were verified using Biovia Discovery studio 4.5. The binding energies of all designed compounds were compared with the standards, Compound RL1 (2-(5-(3-carbamoyl-1H-1,2,4-triazol-1-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)-carbonyl)amino)(hydroxy)methyl)carbamoyl)phenyl acetate) and Compound FL2 (8-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-6-yl(2-(6-flouro-3-oxo-3,4-dihydropyrazine-2-carboxamido)-1-hydroxy-3-phenylpropyl)carbamate) proved to be promising agents with strong binding interactions. Hybrid molecules that inhibit viral replication, possibly as transition state inhibitors, can be investigated further for use in the treatment of SARS-Co-V infection and its associated complications

Combination effect of silymarin, quercetin, and hesperidin on anxiety and depression in 3 nitropropionic acid-induced rat model of huntington’s disease

Huntington’s disease is an autosomal-dominant, progressive neurodegenerative disorder with chorea, incoordination, cognitive decline, and behavioral difficulties, whereas bioflavonoids have the potential to promote anxiety and depression. The aim of this study was to investigate and summarize the synergistic effect of silymarin, quercetin, and hesperidin on anxiety and depression in 3-nitropropionic acid (3-NP)-induced rat model of Huntington’s disease. We divided animals into eight groups (n = 6) for different combination treatment with said bioflavonoids along with 3-NP. Anxiety and depression such as symptoms were assessed on 21st day post-treatment with elevated plus maze, light, and dark model and force swim test. Dopamine and serotonin level in the brain striatum were also measured after completion of behavioral analysis as these neurotransmitters are involved in anxiety and depression like behavior. We found that intraperitoneal administration of 3-NP (10 mg/kg B/W) for 21 days leads to anxiety and depression such as symptoms in male Wistar rats, whereas combinations of bioflavonoids ameliorate the symptoms. At the end of the study, we concluded that combination of silymarin, quercetin, and hesperidin is more effective in ameliorating anxiety and depression as compared to mono therapy