Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors. Issue 9 (1st May 2019)

• Record Type: Journal Article
• Authors: Desai, Dhimant; Lauver, Matthew; Ostman, Alexandria; Cruz, Linda; Ferguson, Kevin; Jin, Ge; Roper, Brianne; Brosius, Daniel; Lukacher, Aron; Amin, Shantu; Buchkovich, Nick
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 9(2019)
• Page Start: 1795
• Page End: 1803
• Publication Date: 2019-05-01
• Subjects: HCMV human cytomegalovirus -- STX5 syntaxin 5 -- MuPyV mouse polyomavirus -- LT large tumor antigen; Human cytomegalovirus -- Mouse polyomavirus -- Antivirals -- Syntaxin 5 -- Retrograde trafficking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.03.026
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.