Paxlovid mouth likely is mediated by activation of the TAS2R1 bitter receptor by nirmatrelvir
Copyright © 2023 Elsevier Inc. All rights reserved..
Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has remained a public health threat since late 2019. Among the strategies rapidly developed to prevent and treat COVID-19, the antiviral medication Paxlovid (nirmatrelvir/ritonavir combination) has shown remarkable efficacy in reducing viral load and relieving clinical symptoms. Unexpectedly, a persistent bitter/bad taste, referred to as "Paxlovid mouth", has been frequently noted. Consistent with this, dysgeusia (altered taste) is listed as a main adverse effect of Paxlovid based on clinical trial data. Nirmatrelvir inhibits Mpro, a SARS-CoV-2 main protease, whereas ritonavir prolongs the activity of nirmatrelvir by slowing its metabolism. Prior usage of ritonavir in other conditions has not been linked to a persistent bad taste, despite the fact that ritonavir tastes bitter. Therefore, we hypothesized that nirmatrelvir may account for Paxlovid mouth by activating one or more of the 25 human TAS2R bitter taste receptors. Here, we show that TAS2R1 is the primary bitter receptor activated by nirmatrelvir, at concentrations as low as 15 μM, which overlaps with plasma concentrations of nirmatrelvir in a subset of patients. We also show that saccharin, a non-nutritive sweetener that may block the activity of TAS2R1, has little or no effect on nirmatrelvir-stimulated TAS2R1 activity. Such findings may help identify novel strategies to alleviate Paxlovid mouth and increase treatment compliance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:682 |
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| Enthalten in: |
Biochemical and biophysical research communications - 682(2023) vom: 19. Nov., Seite 138-140 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Caronia, Lauren [VerfasserIn] |
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| Links: |
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| Themen: |
Antiviral Agents |
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| Anmerkungen: |
Date Completed 01.11.2023 Date Revised 05.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2023.10.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362998434 |
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| 520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
| 520 | |a Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has remained a public health threat since late 2019. Among the strategies rapidly developed to prevent and treat COVID-19, the antiviral medication Paxlovid (nirmatrelvir/ritonavir combination) has shown remarkable efficacy in reducing viral load and relieving clinical symptoms. Unexpectedly, a persistent bitter/bad taste, referred to as "Paxlovid mouth", has been frequently noted. Consistent with this, dysgeusia (altered taste) is listed as a main adverse effect of Paxlovid based on clinical trial data. Nirmatrelvir inhibits Mpro, a SARS-CoV-2 main protease, whereas ritonavir prolongs the activity of nirmatrelvir by slowing its metabolism. Prior usage of ritonavir in other conditions has not been linked to a persistent bad taste, despite the fact that ritonavir tastes bitter. Therefore, we hypothesized that nirmatrelvir may account for Paxlovid mouth by activating one or more of the 25 human TAS2R bitter taste receptors. Here, we show that TAS2R1 is the primary bitter receptor activated by nirmatrelvir, at concentrations as low as 15 μM, which overlaps with plasma concentrations of nirmatrelvir in a subset of patients. We also show that saccharin, a non-nutritive sweetener that may block the activity of TAS2R1, has little or no effect on nirmatrelvir-stimulated TAS2R1 activity. Such findings may help identify novel strategies to alleviate Paxlovid mouth and increase treatment compliance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Bitter | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Nirmatrelvir | |
| 650 | 4 | |a Paxlovid | |
| 650 | 4 | |a TAS2Rs | |
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| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Xi, Ranhui |e verfasserin |4 aut | |
| 700 | 1 | |a Margolskee, Robert F |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Peihua |e verfasserin |4 aut | |
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