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Bio
Central to the multiplication of positive-strand RNA viruses is the virus-encoded RNA-dependent RNA polymerase (RdRp). This enzyme, therefore, represents an attractive target for the development of antivirals. To gain a better understanding of this class of polymerase, over the past several years we have developed novel strategies that provide information on the kinetic, thermodynamic, and structural basis for fidelity of nucleotide incorporation. This has allowed us to obtain key insights into the chemical mechanism for nucleotidyl transfer, discovery of a link between RdRp incorporation fidelity and pathogenesis, uncovering of a connection between RdRp dynamics and incorporation fidelity; identifying a correlation between RdRp infidelity and the frequency of RNA recombination; and discovery of novel mechanisms of RdRp inhibition critical to the development of antiviral ribonucleotides. Our initial focus was on viruses that encode a single-subunit RdRp, we are now including viruses that have more complex multi-subunit viral replicases-this includes flaviviruses, alphaviruses and coronaviruses.
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Papers共 117 篇Author StatisticsCo-AuthorSimilar Experts
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Eric M Merten, John D Sears,Tina M Leisner, Paul B Hardy, Anirban Ghoshal,Mohammad Anwar Hossain,Kesatebrhan Haile Asressu,Peter J Brown,Michael A Stashko,Laura Herring,Angie L Mordant, Thomas S Webb,
bioRxiv : the preprint server for biology (2024)
Acta Crystallographica Section A Foundations and Advancesno. a2 (2023)
Journal of Biological Chemistryno. 3 (2023): 103582-103582
Haley S Caldwell,Lili Kuo,Janice D Pata,Alan P Dupuis,Jamie J Arnold, Calvin Yeager,Jessica Stout,Cheri A Koetzner, Anne F Payne,Sean M Bialosuknia,Elyse M Banker, Taylor A Nolen,
Biophysical journalno. 3S1 (2023): 171a-171A
PLOS Biology (2022)
Nucleic Acids Researchno. 3 (2022): S298-S298
Molecular cellno. 21 (2021): 4467-4480.e7
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