The Life Cycle and in silico Elucidation of Non-structural Replicating Proteins of HCV Through a Pharmacoinformatics Approach.

BACKGROUND: Hepatitis C virus (HCV) is an enveloped and positive-stranded RNA virus that is a major causative agent of chronic liver diseases worldwide. HCV has become the main cause of liver transplantations and there is no effective drug for all hepatitis genotypes. Elucidation of the life cycle and non-structural proteins of HCV, involved in viral replication, are attractive targets for the development of antiviral drugs.. METHODS: In this work, pharmacoinformatics approaches coupled with docking analyses were applied on HCV non-structural proteins to identify the novel potential hits and HCV drugs. Molecular docking analyses were carried out on HCV-approved drugs, followed by the ligandbased pharmacophore generation to screen the antiviral libraries for novel potential hits. RESULTS: Virtual screening technique has top-ranked five novel compounds (ZINC00607900, ZINC03635748, ZINC03875543, ZINC04097464, and ZINC12503102) along with their least binding energies (-8.0 kcal/mol, -6.1 kcal/mol, -7.5 kcal/mol, -7.4 kcal/mol, and -7.3 kcal/mol, respectively) and stability with the non-structural proteins target. CONCLUSION: These promising hits exhibited better absorption and ADMET properties as compared to the selected drug molecules. These potential compounds extracted from in silico approach may be significant in drug design and development against Hepatitis and other liver diseases.

Results of endoscopic endonasal dacryocystorhinostomy: A prospective cohort study.

OBJECTIVE: To evaluate the success rate of endoscopic endonasal dacryocystorhinostomy. METHODS: The prospective cohort study was conducted at the Ophthalmology and Otorhinolaryngology departments, Shifa Foundation Community Health Centre, Islamabad, Pakistan, from October 2017 to September 2019, and comprised chronic dacryocystitis patients who underwent endoscopic endonasal dacryocystorhinostomy. Endoscopic dacryocystorhinostomy with or without lacrimal intubation was performed under general anaesthesia. The patients were followed up post-operative at 1 week, 1 month, 6 months and 12 months. Data was analysed using SPSS 20. RESULTS: Of the 47 patients, 41(87.2%) were females. The overall mean age was 40.70±10.84 years (range: 25-66 years). Lacrimal intubation was performed in 31(66%) patients. Surgical success was achieved in 46(97.9%) patients. Of them, 37(78.7%) patients were completely symptom-free, while 9(19.1%) were partially symptomatic and were managed conservatively. Treatment failure requiring repeat surgical procedure was the case with 1(2.1%) patient. Procedure failure was more likely in patients with previous attacks of acute dacryocystitis (p=0.003). CONCLUSIONS: Endoscopic dacryocystorhinostomy was found to be a safe procedure with good anatomical and functional outcomes in chronic dacryocystitis patients.