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An “All-In-One” Pharmacophoric Architecture for the Discovery of Potential Broad-Spectrum Anti-Flavivirus Drugs

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A precipitous increase in the number of flaviviral infections has been noted over the last 5 years. Despite these outbreaks, treatment protocols for infected individuals remain ambiguous. Numerous studies have identified… Click to show full abstract

A precipitous increase in the number of flaviviral infections has been noted over the last 5 years. Despite these outbreaks, treatment protocols for infected individuals remain ambiguous. Numerous studies have identified NITD008 as a potent flavivirus inhibitor; however, clinical testing was dismissed due to undesirable toxic effects. The binding landscape of NITD008 in complex with five detrimental flaviviruses at the RNA-dependent RNA polymerase active sites was explored. An “all-in-one” pharmacophore model was created for the design of small molecules that may inhibit a broad spectrum of flaviviruses. This pharmacophore model approach serves as a robust cornerstone, thus assisting medicinal experts in the composition of multifunctional inhibitors that will eliminate cross-resistance and toxicity and enhance patient adherence.

Keywords: discovery potential; spectrum; pharmacophoric architecture; one pharmacophoric; broad spectrum; architecture discovery

Journal Title: Applied Biochemistry and Biotechnology
Year Published: 2018

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