Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors

Dhimant Desai, Matthew Lauver, Alexandria Ostman, Linda Cruz, Kevin Ferguson, Ge Jin, Brianne Roper, Daniel Brosius, Aron Lukacher, Shantu Amin, Nick Buchkovich

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1795-1803
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume27
Issue number9
DOIs
StatePublished - May 1 2019

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this