A standardized approach to the evaluation of antivirals against DNA viruses: Polyomaviruses and lymphotropic herpesviruses

• Published in: Antiviral research Vol. 159; pp. 122 - 129
• Main Authors: Keith, Kathy A., Hartline, Caroll B., Bowlin, Terry L., Prichard, Mark N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2018
• Subjects: Antiviral Agents - pharmacology; Automation, Laboratory; DNA, Viral - analysis; Drug Discovery - methods; Drug Discovery - standards; Herpesviridae - drug effects; Humans; Nucleosides - pharmacology; Polyomavirus - drug effects; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2018.09.016

The search for new compounds with a broad spectrum of antiviral activity is important and requires the evaluation of many compounds against several distinct viruses. Researchers attempting to develop new antiviral therapies for DNA virus infections currently use a variety of cell lines, assay conditions and measurement methods to determine in vitro drug efficacy, making it difficult to compare results from within the same laboratory as well as between laboratories. In this paper, we describe the assessment of antiviral activity of a set of nucleoside analogs against BK polyomavirus, JC polyomavirus, Epstein-Barr virus, human herpesvirus 6B, and human herpesvirus 8 in an automated 384-well format and utilize qPCR assays to measure the accumulation of viral DNA. In an accompanying paper, we present a standardized approach to evaluating antivirals against additional herpesviruses, orthopoxviruses, and adenovirus. Together, they reveal new activities for reference compounds and help to define the spectrum of antiviral activity for a set of nucleoside analogs against a set of 12 DNA viruses that infect humans including representative human herpesviruses, orthopoxviruses, adenoviruses, and polyomaviruses. This analysis helps provide perspective on combinations of agents that would help provide broad coverage of significant pathogens in immunocompromised patients as well as against emerging infections. •Automated antiviral assays in 384-well plates are presented for 5 viruses including EBV, HHV-6B, HHV-8, BKPyV and JCPyV.•Efficacy is presented for 7 reference compounds including cidofovir, foscarnet, ganciclovir, acyclovir, and filociclovir.•Spectrum of antiviral activity for compounds against 12 viruses from four families of DNA viruses are presented.•New activities were detected for some compounds including the inhibition of adenovirus replication by filociclovir.