Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 27, Issue 9, Pages 1795-1803Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.03.026
Keywords
Human cytomegalovirus; Mouse polyomavirus; Antivirals; Syntaxin 5; Retrograde trafficking
Funding
- W.W. Smith Charitable Trust
- Penn State Cancer Institute
- National Institutes of Health [NS088367, NS092662]
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Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses.
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