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Antiviral research

Antiviral research

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Antiviral activities of two nucleos(t)ide analogs against vaccinia, mpox, and cowpox viruses in primary human fibroblasts

Published:1 August 2023 DOI: 10.1016/j.antiviral.2023.105651 PMID: 37270160
Lara Dsouza , Anil Pant , Samuel Offei , Lalita Priyamvada , Blake Pope , Panayampalli S. Satheshkumar , Zhengqiang Wang , Zhilong Yang

Abstract

Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox (formerly monkeypox). Identifying novel and potent antiviral compounds is critical to successful drug development targeting poxviruses. Here we tested two compounds, nucleoside trifluridine, and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV), mpox virus (MPXV), and cowpox virus (CPXV) in physiologically relevant primary human fibroblasts. Both compounds potently inhibited the replication of VACV, CPXV, and MPXV (MA001 2022 isolate) in plaque assays. In our recently developed assay based on a recombinant VACV expressing secreted Gaussia luciferase, they both exhibited high potency in inhibiting VACV replication with EC50s in the low nanomolar range. In addition, both trifluridine and adefovir dipivoxil inhibited VACV DNA replication and downstream viral gene expression. Our results characterized trifluridine and adefovir dipivoxil as strong poxvirus antiviral compounds and further validate the VACV Gaussia luciferase assay as a highly efficient and reliable reporter tool for identifying poxvirus inhibitors. Given that both compounds are FDA-approved drugs, and trifluridine is already used to treat ocular vaccinia, further development of trifluridine and adefovir dipivoxil holds great promise in treating poxvirus infections, including mpox.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Adefovir dipivoxil 142340-99-6 C20H32N5O8P 614 suppliers $5.00-$1599.00
Adefovir dipivoxil 142340-99-6 C20H32N5O8P 614 suppliers $5.00-$1599.00
Adefovir dipivoxil 142340-99-6 C20H32N5O8P 614 suppliers $5.00-$1599.00
Adefovir dipivoxil 142340-99-6 C20H32N5O8P 614 suppliers $5.00-$1599.00
Trifluridine 70-00-8 C10H11F3N2O5 452 suppliers $8.00-$2400.00
Trifluridine 70-00-8 C10H11F3N2O5 452 suppliers $8.00-$2400.00
Trifluridine 70-00-8 C10H11F3N2O5 452 suppliers $8.00-$2400.00
Trifluridine 70-00-8 C10H11F3N2O5 452 suppliers $8.00-$2400.00
CMX 001 444805-28-1 C27H52N3O7P 109 suppliers Inquiry
CMX 001 444805-28-1 C27H52N3O7P 109 suppliers Inquiry

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