A. J. Parsons, Tobias S D Cohen, T. Schwarz
Jun 28, 2021
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Influential Citations
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Quality indicators
Journal
Antiviral research
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that establishes a life-long infection affecting up to 80% of the US population. HCMV periodically reactivates leading to enhanced morbidity and mortality in immunosuppressed patients causing a range of complications including organ transplant failure and cognitive disorders in neonates. Therapeutic options for HCMV are limited to a handful of antivirals that target late stages of the virus life cycle and efficacy is often challenged by the emergence of mutation which confer resistance. In addition, these antiviral therapies have several adverse reactions including neutropenia in newborns and in increase in adverse cardiac events in HSCT patients. These findings highlight the need to develop novel therapeutics that target different steps of the viral life cycle. To this end, we screened a small molecule library against ion transporters to identify new antivirals against the early steps of virus infection. We identified valspodar, a 2nd-generation inhibitor characterized to target ABC transporters, to limit HCMV infection as demonstrated by the decrease in IE2 expression of virus infected cells. Cells treated with increasing concentrations of valspodar over a 6-day period have minimal cytotoxicity. Importantly, valspodar limits CMV plaque numbers in comparison to DMSO controls demonstrating its ability to inhibit viral dissemination. Collectively, valspodar represents a new anti-CMV therapeutic that limits CMV infection by likely targeting a host factor and suggests that specific ABC transporters may participate in the HCMV life-cycle.