D
Dustin Siegel
Publications - 32
Citations - 3785
Dustin Siegel is an academic researcher. The author has contributed to research in topics: Ebola virus & Pneumovirinae. The author has an hindex of 12, co-authored 31 publications receiving 2979 citations.
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Journal ArticleDOI
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses
Timothy P. Sheahan,Amy C. Sims,Rachel L. Graham,Vineet D. Menachery,Lisa E. Gralinski,James Brett Case,Sarah R. Leist,Krzysztof Pyrc,Joy Y. Feng,Iva Trantcheva,Roy Bannister,Yeojin Park,Darius Babusis,Michael O. Clarke,Richard L. Mackman,Jamie E. Spahn,Christopher A. Palmiotti,Dustin Siegel,Adrian S. Ray,Tomas Cihlar,Robert Jordan,Mark R. Denison,Ralph S. Baric +22 more
TL;DR: Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses in vitro and in vivo and may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and, possibly most importantly, emerging CoV of the future.
Journal ArticleDOI
Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease
Maria L. Agostini,Erica L. Andres,Amy C. Sims,Rachel L. Graham,Timothy P. Sheahan,Xiaotao Lu,Everett Clinton Smith,Everett Clinton Smith,James Brett Case,Joy Y. Feng,Robert Jordan,Adrian S. Ray,Tomas Cihlar,Dustin Siegel,Richard L. Mackman,Michael O'neil Hanrahan Clarke,Ralph S. Baric,Mark R. Denison +17 more
TL;DR: It is shown that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC50) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS- coV) and that resistance can be overcome with increased, nontoxic concentrations of GS- 5734, further supporting the development of GS -5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.
Journal ArticleDOI
Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses
Dustin Siegel,Hui Hon Chung,Edward Doerffler,Michael O'neil Hanrahan Clarke,Kwon Soo Chun,Lijun Zhang,Sean Neville,Ernest Carra,Willard Lew,Bruce Ross,Queenie Wang,Lydia Wolfe,Robert Jordan,Veronica Soloveva,John E. Knox,Jason K. Perry,Michel Perron,Kirsten M. Stray,Ona Barauskas,Joy Y. Feng,Yili Xu,Gary Lee,Arnold L. Rheingold,Adrian S. Ray,Roy Bannister,Robert G. Strickley,S. Swaminathan,William A. Lee,Sina Bavari,Tomas Cihlar,Michael K. Lo,Travis K. Warren,Richard L. Mackman +32 more
TL;DR: A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model and structure activity relationships established that the 1′-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases.
Journal ArticleDOI
GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses.
Michael K. Lo,Robert Jordan,Aaron Arvey,Jawahar Sudhamsu,Punya Shrivastava-Ranjan,Anne L. Hotard,Mike Flint,Laura K. McMullan,Dustin Siegel,Michael O. Clarke,Richard L. Mackman,Hui Hon Chung,Michel Perron,Adrian S. Ray,Tomas Cihlar,Stuart T. Nichol,Christina F. Spiropoulou +16 more
TL;DR: The antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families are reported, providing evidence to support new indications for this compound against human viruses of significant public health concern.
Journal ArticleDOI
Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study
Richard L. Mackman,Sangi Michael,David Sperandio,Jay P. Parrish,Eugene J. Eisenberg,Michel Perron,Hui Hon Chung,Lijun Zhang,Dustin Siegel,Hai Yang,Oliver L. Saunders,Constantine G. Boojamra,Gary Lee,Dharmaraj Samuel,Kerim Babaoglu,Anne Carey,Brian E. Gilbert,Pedro A. Piedra,Robert G. Strickley,Quynh Iwata,Jaclyn Hayes,Kirsten M. Stray,April Kinkade,Dorothy Agnes Theodore,Robert Jordan,Manoj C. Desai,Tomas Cihlar +26 more
TL;DR: A potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV infection in infants and adults is reported.