In 2013 Gilead established the sponsorship for the Antonín Holý Memorial Award, in recognition of the major contributions of Dr. Holý to antiviral medicine, best represented by the phosphonate class of antivirals. This Award was then established by ISAR to recognize a senior medicinal chemist scientist of international stature who has had major impacts in antiviral drug discovery or development. The first Awardee was Piet Herdewijn in 2014. Through the years, this Award has been bestowed on such renown medicinal chemists as Robert Vince, CK (David) Chu, Dennis Liotta, Chris Mejer, Richard Mackman, and ISAR’s current president elect, Katherine (Kathie) Seley-Radtke. For 2021, ISAR has bestowed the Antonin Holy Memorial Award to Dr. Eddy Arnold.
Eddy Arnold’s laboratory at the Center for Advanced Biotechnology and Medicine (CABM) and Rutgers University works to understand the structural and molecular basis of the chemistry underlying life. A major focus is placed on studying human disease related problems and then applying the insights gained to the development of better treatments.
His research has profoundly influenced our understanding of the structure and biological function of viruses and their components. The cross-disciplinary research in Arnold’s group uses a broad swath of tools and techniques from molecular biology, protein chemistry and biochemistry, biophysics, virology, crystallography, cryo-EM, and computational chemistry. Eddy’s work has illuminated fundamental molecular mechanisms of viral polymerase structure and function, infection and escape from antiviral drugs and immune surveillance, and protein-nucleic acid and protein-ligand interactions. His efforts in Michael Rossmann’s laboratory culminated in elucidating the structure of a common cold virus, the first animal virus described in complete atomic detail. Eddy’s structure of HIV reverse transcriptase complexed with DNA, the first polymerase visualized with a relevant substrate, changed the landscape of the HIV/AIDS and polymerase biochemistry fields. Arnold’s longstanding collaboration with Stephen Hughes has resulted in extraordinarily diverse and innovative studies of HIV reverse transcriptase structure, function, inhibition, and resistance that have helped to make this critical enzyme the most thoroughly understood of any DNA polymerase.
Arnold’s efforts with legendary drug developer Dr. Paul Janssen, enabled the design and discovery of five anti-AIDS drugs that are broadly used for treating HIV-infected patients and are resilient to drug resistance. Arnold’s team developed the strategic flexibility hypothesis, which postulates that structural flexibility and compactness of inhibitors can overcome resistance to mutations, a concept that can be applied to any disease target. His elegant analyses of the RT inhibition mechanisms by AZT and nevirapine have likewise spawned generalizable principles. Crystallographic fragment screening efforts identified novel allosteric inhibitory sites in HIV-1 reverse transcriptase and led to new classes of antiviral inhibitors targeting influenza virus endonuclease and HIV-1 integrase. Arnold’s work with Richard Ebright on multi-subunit bacterial RNA polymerase visualized aspects of transcription relevant to all living organisms and elucidated binding modes for multiple new classes of potential antibiotics.
Dr. Arnold will give one of the keynote lectures at the upcoming virtual ICAR2021, when he will talk about the 35 years of work on the HIV reverse transcriptase and its inhibitors, with an emphasis on the successes in antiretroviral therapy. Please join us congratulating Dr. Arnold and don’t miss the opportunity to attend his lecture at the virtual 2021 ICAR meeting- we’ll see you there!
January 11, 2021
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