02575nas a2200325   4500008004100000245017700041210006900218260000800287300000800295490000700303520150700310653001401817653001301831653001601844653001501860653001501875653001501890100001901905700002401924700002201948700001701970700002301987700001802010700001802028700001602046700002102062700001802083700002202101856012602123       2023                        eng d00aComprehensive molecular and clinical investigation of approved Anti-HCV drugs repurposing against SARS-CoV-2 infection: a glaring gap between benchside and bedside medicine0 aComprehensive molecular and clinical investigation of approved A  cMAR  a5150 v113 a<p>
	The limited availability of effective treatment against SARS-CoV-2 infection is a major challenge in managing COVID-19. This scenario has augmented the need for repurposing anti-virals for COVID-19 mitigation. In this report, the anti-SARS-CoV-2 potential of anti-HCV drugs such as daclatasvir (DCV) or ledipasvir (LDP) in combination with sofosbuvir (SOF) was evaluated. The binding mode and higher affinity of these molecules with RNA-dependent-RNA-polymerase of SARS-CoV-2 were apparent by computational analysis. In vitro anti-SARS-CoV-2 activity depicted that SOF/DCV and SOF/LDP combination has IC50 of 1.8 and 2.0 mu M, respectively, comparable to remdesivir, an approved drug for COVID-19. Furthermore, the clinical trial was conducted in 183 mild COVID-19 patients for 14 days to check the efficacy and safety of SOF/DCV and SOF/LDP compared to standard of care (SOC) in a parallel-group, hybrid, individually randomized, controlled clinical study. The primary outcomes of the study suggested no significant difference in negativity after 3, 7 and 14 days in both treatments. None of the patients displayed any worsening in the disease severity, and no mortality was observed in the study. Although, the post hoc exploratory analysis indicated significant normalization of the pulse rate showed in SOF/DCV and SOF/LDP treatment vs. SOC. The current study highlights the limitations of bench side models in predicting the clinical efficacy of drugs that are planned for repurposing.</p>
10aantiviral10aCOVID-1910adaclatasvir10aledipasvir10aSARS-CoV-210asofosbuvir1 aBansode, Sneha1 aSingh, Pawan, Kumar1 aTellis, Meenakshi1 aChugh, Anita1 aDeshmukh, Narendra1 aGupta, Mahesh1 aVerma, Savita1 aGiri, Ashok1 aKulkarni, Mahesh1 aJoshi, Rakesh1 aChaudhary, Dhruva  uhttps://library.ncl.res.in/content/comprehensive-molecular-and-clinical-investigation-approved-anti-hcv-drugs-repurposing