Abstract
Dengue virus (DENV) is the causative agent of dengue fever. Annually, there are about 400 million new cases of dengue worldwide, and so far there is no specific treatment against this disease. The NS5 protein is the largest and most conserved viral protein among flaviviruses and is considered a therapeutic target of great interest. This study aims to search drug-like compounds for possible inhibitors of the NS5 protein in the four serotypes of DENV. Using a virtual screening from a ∼642,759-compound database, we suggest 18 compounds with NS5 binding and highlight the best compound per region, in the methyltransferase and RNA-dependent RNA polymerase domains. These compounds interact mainly with the amino acids of the catalytic sites and/or are involved in processes of protein activity. The identified compounds presented physicochemical and pharmacological properties of interest for their use as possible drugs; furthermore, we found that some of these compounds do not affect cell viability in Huh-7; therefore, we suggest evaluating these compounds in vitro as candidates in future research.
Highlights
Dengue virus (DENV) is a member of the genus Flavivirus belonging to the family Flaviviridae (Zou et al, 2011; Lim et al, 2013a)
Our results suggest that compound 1md prefers the DENV3 and DENV4 serotypes over the other two serotypes, with DENV3 and DENV4 being the serotypes with the highest ΔGbind values
We performed a computational screening of several drug-like compounds with potential effects against the NS5 protein of the dengue virus
Summary
Dengue virus (DENV) is a member of the genus Flavivirus belonging to the family Flaviviridae (Zou et al, 2011; Lim et al, 2013a). DENV is the causative agent of the viral disease known as dengue fever, which is transmitted through the bite of mosquito species Aedes aegypti and Aedes albopictus (Regato et al, 2008; Basavannacharya and Vasudevan., 2014). This disease mainly affects people who live in tropical and subtropical countries, with approximately 400 million new cases worldwide annually, and can lead to febrile illness and flu-like symptoms or can progress to the more severe dengue hemorrhagic fever or dengue shock syndrome (Klema et al, 2016). In the last years, the presence of a fifth serotype with a sylvatic cycle was reported (Mustafa et al, 2014)
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