An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever

Powers, Chelsea N.; Setzer, William N.

Dengue fever is an acute viral infection caused by all four serotypes (1, 2, 3, or 4) of the dengue virus (DENV), and is one of the seventeen "Neglected Tropical Diseases" (NTDs) defined by the World Health Organization [1] . The highest incidence of dengue fever is in Southeast Asia, India, and the Neotropics; where the principal vector, the Aedes aegypti mosquito, is found [2] . There are two well defined manifestations of dengue virus infection in humans, dengue fever and severe dengue (dengue hemorrhagic fever / dengue shock syndrome, DHF/DSS) [3] . Dengue viral infections account for around 100 million cases of dengue fever and more than 500,000 cases of DHF/DSS each year [4] . India accounts for around 34% of the total global dengue infections while tropical America contributes around 14% [1, 5] . Delhi, India has had several epidemic outbreaks of dengue fever (1970, 1982, 1988, 1996, 2006, 2010, and 2013) [6] . In the 2013 outbreak, 71% of suspected patients tested positive for dengue virus, mainly DENV-2, but coinfection by different serotypes was also detected [7] . Rio de Janeiro, Brazil, has suffered similar epidemic outbreaks of dengue fever (1986, 1990, 2001-02, 2007-08, 2011, and 2012) [8, 9] . Between 2010 and 2012, dengue virus infection was confirmed in 47.5% of the cases; DENV-2 the prevalent serotype in 2010, but DENV-1 re-emerged as the major *Address correspondence to this author at the Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA; Tel: [phone]; Fax: [phone]; E-mail: [e-mail] serotype in 2011 [9] . In addition, between 2010 and 2012, 7.3% of the cases were severe (DHF/DSS), due mainly to secondary dengue infection. In 2007, 53% of DHF/DSS cases occurred in children under 15 years of age [10] . Furthermore, a correlation between increased dengue infection risk and socioeconomic status has been demonstrated; poorer inhabitants with poor access to health services showed a significantly higher seroprevelence compared to wealthy inhabitants [10, 11] . A serological survey carried out in 2007-2008 in three neighborhoods of Rio de Janeiro showed more than half the population was seropositive (60.3% in Higienópolis, a densely populated urban neighborhood, 56.1% in Tubiacanga, a suburban residential neighborhood, and 77.4% in Palmares, a recently settled slum) [8] .