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Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase

Steffen Jockusch, Chuanjuan Tao, Xiaoxu Li, Thomas K. Anderson, Minchen Chien, Shiv Kumar, James J. Russo, Robert N. Kirchdoerfer, Jingyue Ju
doi: https://doi.org/10.1101/2020.04.03.022939
Steffen Jockusch
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
2Departments of Chemistry, Columbia University, New York, NY 10027
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Chuanjuan Tao
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
3Departments of Chemical Engineering, Columbia University, New York, NY 10027
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Xiaoxu Li
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
3Departments of Chemical Engineering, Columbia University, New York, NY 10027
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Thomas K. Anderson
5Departments of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
6Institute of Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706
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Minchen Chien
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
3Departments of Chemical Engineering, Columbia University, New York, NY 10027
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Shiv Kumar
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
3Departments of Chemical Engineering, Columbia University, New York, NY 10027
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James J. Russo
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
3Departments of Chemical Engineering, Columbia University, New York, NY 10027
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Robert N. Kirchdoerfer
5Departments of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
6Institute of Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706
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  • For correspondence: dj222@columbia.edu rnkirchdoerf@wisc.edu
Jingyue Ju
1Center for Genome Technology and Biomolecular Engineering, Columbia University, New York, NY 10027
3Departments of Chemical Engineering, Columbia University, New York, NY 10027
4Departments of Pharmacology, Columbia University, New York, NY 10027
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  • For correspondence: dj222@columbia.edu rnkirchdoerf@wisc.edu
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Abstract

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. We previously demonstrated that four nucleotide analogues (specifically, the active triphosphate forms of Sofosbuvir, Alovudine, AZT and Tenofovir alafenamide) inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Tenofovir and emtricitabine are the two components in DESCOVY and TRUVADA, the two FDA-approved medications for use as pre-exposure prophylaxis (PrEP) to prevent HIV infection. This is a preventative method in which individuals who are HIV negative (but at high-risk of contracting the virus) take the combination drug daily to reduce the chance of becoming infected with HIV. PrEP can stop HIV from replicating and spreading throughout the body. We report here that the triphosphates of tenofovir and emtricitabine, the two components in DESCOVY and TRUVADA, act as terminators for the SARS-CoV-2 RdRp catalyzed reaction. These results provide a molecular basis to evaluate the potential of DESCOVY and TRUVADA as PrEP for COVID-19.

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Posted April 05, 2020.
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Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase
Steffen Jockusch, Chuanjuan Tao, Xiaoxu Li, Thomas K. Anderson, Minchen Chien, Shiv Kumar, James J. Russo, Robert N. Kirchdoerfer, Jingyue Ju
bioRxiv 2020.04.03.022939; doi: https://doi.org/10.1101/2020.04.03.022939
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Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase
Steffen Jockusch, Chuanjuan Tao, Xiaoxu Li, Thomas K. Anderson, Minchen Chien, Shiv Kumar, James J. Russo, Robert N. Kirchdoerfer, Jingyue Ju
bioRxiv 2020.04.03.022939; doi: https://doi.org/10.1101/2020.04.03.022939

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