Zika virus is a mosquito-borne disease originally discovered in primates in the late 1940’s in Africa. Recent (2014-present) outbreaks in South America and several pacific islands have prompted the World Health Organization (WHO) to recognize Zika as a dangerous, mosquito-borne disease prevalent in tropical and subtropical regions around the world. While most presentations in adults are generally mild and include fever, rash, headaches, and muscle and joint pain, the flavivirus has the potential to manifest microcephaly and Guillian-Barre syndrome in the fetuses of pregnant women.  This study proposes to use virtual screening methods to target the viral entry protein glycoprotein E, a protein analogous to those in HIV and Ebola, in conjunction with a new <i>de novo</i> design method termed NOVA (Navigation and Optimization for Virtual Assembly) that constructs inhibitor candidates from scratch. The appeal of a two-pronged computational approach is the ability to generate hits with more chemical diversity than might be possible using either approach alone.  Per-residue footprints have been used to identify compounds between the two sampling methods that make comparable electrostatic and Van der Waals interactions, and visual inspection indicates that common chemical moieties are positioned at similar locations relative to the binding site explored thus far. To date, 53 compounds have been experimentally characterized and several molecules are being further investigated as potential lead compounds.<br/>

Orthogonal approach to computational biomolecular screening: Application to glycoprotein E of Zika virus

256th National Meeting (2018)

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