Valspodar limits human cytomegalovirus infection and dissemination.

TitleValspodar limits human cytomegalovirus infection and dissemination.
Publication TypeJournal Article
Year of Publication2021
AuthorsParsons AJ, Cohen T, Schwarz TM, Stein KR, Ophir SI, Casado JParedes, Tortorella D
JournalAntiviral Res
Date Published2021 Sep
KeywordsAntiviral Agents, ATP-Binding Cassette Transporters, Cell Line, Cells, Cultured, Cyclosporins, Cytomegalovirus, Cytomegalovirus Infections, Humans, Microbial Sensitivity Tests, Virus Internalization, Virus Replication

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 mutations that confer resistance. In addition, these antiviral therapies may have adverse reactions including neutropenia in newborns and an 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 ABC transporter inhibitor, that limits HCMV infection as demonstrated by the decrease in IE2 expression of virus infected cells. Cells treated with increasing concentrations of valspodar over a 9-day period show minimal cytotoxicity. Importantly, valspodar limits HCMV plaque numbers in comparison to DMSO controls demonstrating its ability to inhibit viral dissemination. Collectively, valspodar represents a potential new anti-HCMV therapeutic that limits virus infection by likely targeting a host factor. Further, the data suggest that specific ABC transporters may participate in the HCMV life-cycle.

Alternate JournalAntiviral Res
PubMed ID34197862
PubMed Central IDPMC9157689
Grant ListR01 AI139258 / AI / NIAID NIH HHS / United States
R21 AI147632 / AI / NIAID NIH HHS / United States
RF1 AG059319 / AG / NIA NIH HHS / United States
T32 AI007647 / AI / NIAID NIH HHS / United States
Related Faculty: 
Tobias Cohen, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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