4.7 Article

Selective Targeting of Virus Replication by Proton Pump Inhibitors

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SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-020-60544-y

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资金

  1. NIH National Institute of General Medical Sciences (NIGMS) [R01 GM111028]
  2. New York State Department of Economic Development/Center for Biotechnology, Stony Brook University [C140151]
  3. NHLBI [U01HL127522]
  4. NHLBI Intramural Research Programs
  5. NIAID [R01 AI113134, R01 AI07521901]
  6. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL001048] Funding Source: NIH RePORTER

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Two proton pump inhibitors, tenatoprazole and esomeprazole, were previously shown to inhibit HIV-1 egress by blocking the interaction between Tsg101, a member of the ESCRT-I complex, and ubiquitin. Here, we deepen our understanding of prazole budding inhibition by studying a range of viruses in the presence of tenatoprazole. Furthermore, we investigate the relationship between the chemistry of prodrug activation and HIV-1 inhibition for diverse prazoles currently on the market. We report that tenatoprazole is capable of inhibiting the replication of members of the enveloped filo, alpha, and herpes virus families but not the flavivirus group and not the non-enveloped poliovirus. Another key finding is that prazole prodrugs must be activated inside the cell, while their rate of activation in vitro correlated to their efficacy in cells. Our study lays the groundwork for future efforts to repurpose prazole-based compounds as antivirals that are both broad-spectrum and selective in nature.

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