@article{8943faaa8a2e495fba5e1058337fbd3e,
title = "Inhibition of diverse opportunistic viruses by structurally optimized retrograde trafficking inhibitors",
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.",
author = "Dhimant Desai and Matthew Lauver and Alexandria Ostman and Linda Cruz and Kevin Ferguson and Ge Jin and Brianne Roper and Daniel Brosius and Aron Lukacher and Shantu Amin and Nick Buchkovich",
note = "Funding Information: We would like to thank Kayla Keller for technical assistance and lab support and Neil Christensen for his generous help in generating a monoclonal antibody used in the assay for titering HCMV infectious virions. We would also like to thank Anne Stanley in the Mass Spectrometry and Proteomics Core Facility and Jyh-Ming Lin of NMR facility at Penn State College of Medicine for MS and NMR, respectively. This work was supported by grants from the H.G. Barsumian M.D. Memorial Fund (N.J.B), the W.W. Smith Charitable Trust (N.J.B, D.D.), the Penn State Cancer Institute (D.D., S.A.) and the National Institutes of Health ( NS088367 and NS092662 (A.E.L)). Funding Information: We would like to thank Kayla Keller for technical assistance and lab support and Neil Christensen for his generous help in generating a monoclonal antibody used in the assay for titering HCMV infectious virions. We would also like to thank Anne Stanley in the Mass Spectrometry and Proteomics Core Facility and Jyh-Ming Lin of NMR facility at Penn State College of Medicine for MS and NMR, respectively. This work was supported by grants from the H.G. Barsumian M.D. Memorial Fund (N.J.B), the W.W. Smith Charitable Trust (N.J.B, D.D.), the Penn State Cancer Institute (D.D. S.A.) and the National Institutes of Health (NS088367 and NS092662 (A.E.L)). Funding Information: We would like to thank Kayla Keller for technical assistance and lab support and Neil Christensen for his generous help in generating a monoclonal antibody used in the assay for titering HCMV infectious virions. We would also like to thank Anne Stanley in the Mass Spectrometry and Proteomics Core Facility and Jyh-Ming Lin of NMR facility at Penn State College of Medicine for MS and NMR, respectively. This work was supported by grants from the H.G. Barsumian M.D. Memorial Fund (N.J.B), the W.W. Smith Charitable Trust (N.J.B, D.D.), the Penn State Cancer Institute (D.D., S.A.) and the National Institutes of Health (NS088367 and NS092662 (A.E.L)). Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2019",
month = may,
day = "1",
doi = "10.1016/j.bmc.2019.03.026",
language = "English (US)",
volume = "27",
pages = "1795--1803",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "9",
}