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عنوان فارسی مقاله:
غربالگری با بازده بالا برای شناسایی مانع ریز مولکول پروتئاز ویروسی
عنوان انگلیسی مقاله:
High-throughput screening for the identification of small-molecule inhibitors of the flaviviral proteas
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
Dengue virus serotypes 1e4 (DENV1-4) cause the most frequent mosquito-borne infections to humans. According to a recent estimate by the World Health Organization, DENVs cause 390 million infections annually (Mitka, 2013), and are primarily transmitted by the Aedes aegypti and A. albopictus mosquitos. Dengue virus (DENV) belongs to the flavivirus genus of the Flaviviridae family and is endemic throughout tropical and sub-tropical countries in the world (for reviews, see (Beasley, 2005; Gould and Solomon, 2008; Guzman et al., 2010; Lindenbach and Rice, 2003)) causing frequent epidemics. Infection with any of the DENV serotypes may be asymptomatic in the majority of cases or may result in a mild flulike syndrome (known as dengue fever (DF). However, secondary infections by a different DENV serotype can cause symptoms collectively known as “severe dengue”, characterized by coagulopathy, increased vascular fragility and permeability, thought to result from antibody-dependent enhancement (Halstead et al., 2005; Sierra et al., 2010). Currently, there is no antiviral drug available for human use. The DENV genome consists of a ~11 kb, plus strand, RNA molecule, that upon entry into a host cell, is translated into a single polyprotein in the endoplasmic reticulum (ER) membrane. This polyprotein undergoes co- and post-translational cleavages by the host signal peptidase and furin, as well as the viral serine protease NS3 to form mature structural and non-structural proteins. The three structural proteins, capsid (C), precursor membrane (prM), and envelope (E), are generated from the N-terminal region of the polyprotein. The seven non-structural (NS) proteins are generated in the order of NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5, from the Cterminal region of the polyprotein (Henchal and Putnak, 1990; Kautner et al., 1997).
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کلمات کلیدی:
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