Ref Nuc 4 Library of Nucleotide Analogues Against
Antiviral Research 180 (2020) 104857 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral Research paper A library of nucleotide analogues terminate RNA synthesis catalyzed by polymerases of coronaviruses that cause SARS and COVID-19 T Steffen Jockuscha,b,1, Chuanjuan Taoa,c,1, Xiaoxu Lia,c,1, Thomas K. Andersone,f, Minchen Chiena,c, ∗∗ ∗ Shiv Kumara,c, James J. Russoa,c, Robert N. Kirchdoerfere,f, , Jingyue Jua,c,d, a Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY, 10027, USA b Department of Chemistry, Columbia University, New York, NY, 10027, USA c Department of Chemical Engineering, Columbia University, New York, NY, 10027, USA d Department of Pharmacology, Columbia University, New York, NY, 10027, USA e Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA f Institute of Molecular Virology, University of Wisconsin-Madison, Madison, WI, 53706, USA ARTICLE INFO ABSTRACT Keywords: SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. COVID-19 We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA SARS-CoV-2 polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir RNA-Dependent RNA polymerase alafenamide and Emtricitabine. We report here the evaluation of a library of nucleoside triphosphate analogues Nucleotide analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These Exonuclease features include modifications on the sugar (2′ or 3′ modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base.
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