Dengue virus (DENV) infections are rampant in tropical and subtropical regions of the world with millions of people at risk. There is still no specific antiviral treatment available against these infections. Amongst the different potential therapeutic targets, DENV protease is considered an important target because of its crucial role in the viral replication cycle. We are reporting here a potent DENV protease inhibitor, eugeniin (3), which has been isolated from cloves, along with two other weaker inhibitors, isobiflorin (1) and biflorin (2). In this study, the IC 50 values of 3 against the proteases of DENV serotype-2 and -3 were found to be 94.7 nM and 7.5 μM, respectively. Mechanistically, the compounds 1−3 exhibited a competitive type of inhibition, which were further substantiated by computational docking and saturation transfer difference (STD) NMR spectroscopy. Atomic-level details of the binding of these molecules at the active site of the protease suggested extensive interactions mediated by a network of hydrogen bonds and hydrophobic contacts. With further evaluation, these inhibitors are highly promising in the context of antiviral therapeutics development against DENV.
Background: Beta thalassemia is the most common genetically transmitted disorder throughout the world. The life of a thalassemia patient depends on continuous blood transfusions, that can lead to various blood-borne viral infections mainly human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections. Nevertheless, HCV infection is the most prevalent among blood transfusion-related blood-borne infections. Co-occurrence of thalassemia major with hepatic fibrosis,severe anemia, and iron over-load complicates HCV treatment. Additionally, treatment of HCV infection generally results in the manifestation of several drug-associated side effects, and the burden of continuous blood transfusions makes the condition worse. Aim: Efficacy and safety of Sofosbuvir/ Daclatasvir in a HCV infected child suffering from thalassemia major. Method: The patient was treated with direct-acting antiviral drugs including Sofosbuvir/ Daclatasvir for twenty weeks. The complete blood count (CBC) and Liver function test (LFT) data were obtained during the whole treatment. The efficacy and safety of treatment was evaluated by CBC and LFT values. The whole data was evaluated by Microsoft excel 2013. Result: No significant side effect was observed during the whole treatment. The hemoglobin (Hb) level remained normal and did not require additional blood transfusion. The end of therapy response (ETR) was achieved after twenty weeks of treatment. Conclusion: Sofosbuvir/ Daclatasvir were found effective in the thalassemia patient. There was no need for dose adjustment. The sustained viral response (SVR24) was achieved.
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