Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry
The pandemic of coronavirus disease 2019 (COVID-19) caused by infection by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to take a huge toll on global health. Although improving, currently there are only limited therapies against SARS-CoV-2. Curcumin, a natural polyphenol, e...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2022.923018/full |
| _version_ | 1811227805942284288 |
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| author | Nabab Khan Zahra Afghah Aparajita Baral Jonathan D. Geiger Xuesong Chen |
| author_facet | Nabab Khan Zahra Afghah Aparajita Baral Jonathan D. Geiger Xuesong Chen |
| author_sort | Nabab Khan |
| collection | DOAJ |
| description | The pandemic of coronavirus disease 2019 (COVID-19) caused by infection by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to take a huge toll on global health. Although improving, currently there are only limited therapies against SARS-CoV-2. Curcumin, a natural polyphenol, exerts antiviral effects against a wide variety of viruses and can inhibit SARS-CoV-2 entry. However, undesirable physicochemical and pharmacokinetic properties of curcumin limit its clinical application. Here, we determined the effects of dimethoxycurcumin (DiMC), a methylated analog of curcumin with improved bioavailability, on the entry of SARS-CoV-2. DiMC blocked entry of pseudo-SARS-CoV-2 into Calu-3 human non-small cell lung adenocarcinoma cells and Vero E6 green monkey kidney epithelial cells. Mechanistically, DiMC acidified lysosomes, enhanced lysosome degradation capabilities, and promoted lysosome degradation of angiotensin converting enzyme 2 (ACE2), a major receptor for SARS-CoV-2 entry, as well as pseudo-SARS-CoV-2 and the SARS-CoV-2 S1 protein. Furthermore, other lysosome acidifying agents, including the TRPML1 agonist ML-SA1 and the BK channel activator NS1619, also blocked the entry of pseudo-SARS-CoV-2. Thus, the anti-SARS-CoV-2 potential of DiMC and lysosome acidifying agents might be explored further as possible effective therapeutic strategies against COVID-19. |
| first_indexed | 2024-04-12T09:48:01Z |
| format | Article |
| id | doaj.art-c5df56ca86d747afbdc23633de8fa609 |
| institution | Directory Open Access Journal |
| issn | 2673-818X |
| language | English |
| last_indexed | 2024-04-12T09:48:01Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj.art-c5df56ca86d747afbdc23633de8fa6092022-12-22T03:37:54ZengFrontiers Media S.A.Frontiers in Virology2673-818X2022-06-01210.3389/fviro.2022.923018923018Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 EntryNabab KhanZahra AfghahAparajita BaralJonathan D. GeigerXuesong ChenThe pandemic of coronavirus disease 2019 (COVID-19) caused by infection by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to take a huge toll on global health. Although improving, currently there are only limited therapies against SARS-CoV-2. Curcumin, a natural polyphenol, exerts antiviral effects against a wide variety of viruses and can inhibit SARS-CoV-2 entry. However, undesirable physicochemical and pharmacokinetic properties of curcumin limit its clinical application. Here, we determined the effects of dimethoxycurcumin (DiMC), a methylated analog of curcumin with improved bioavailability, on the entry of SARS-CoV-2. DiMC blocked entry of pseudo-SARS-CoV-2 into Calu-3 human non-small cell lung adenocarcinoma cells and Vero E6 green monkey kidney epithelial cells. Mechanistically, DiMC acidified lysosomes, enhanced lysosome degradation capabilities, and promoted lysosome degradation of angiotensin converting enzyme 2 (ACE2), a major receptor for SARS-CoV-2 entry, as well as pseudo-SARS-CoV-2 and the SARS-CoV-2 S1 protein. Furthermore, other lysosome acidifying agents, including the TRPML1 agonist ML-SA1 and the BK channel activator NS1619, also blocked the entry of pseudo-SARS-CoV-2. Thus, the anti-SARS-CoV-2 potential of DiMC and lysosome acidifying agents might be explored further as possible effective therapeutic strategies against COVID-19.https://www.frontiersin.org/articles/10.3389/fviro.2022.923018/fulldimethoxycurcuminACE2 (angiotensin converting enzyme-2)lysosomeacidificationSARS-CoV-2 |
| spellingShingle | Nabab Khan Zahra Afghah Aparajita Baral Jonathan D. Geiger Xuesong Chen Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry Frontiers in Virology dimethoxycurcumin ACE2 (angiotensin converting enzyme-2) lysosome acidification SARS-CoV-2 |
| title | Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry |
| title_full | Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry |
| title_fullStr | Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry |
| title_full_unstemmed | Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry |
| title_short | Dimethoxycurcumin Acidifies Endolysosomes and Inhibits SARS-CoV-2 Entry |
| title_sort | dimethoxycurcumin acidifies endolysosomes and inhibits sars cov 2 entry |
| topic | dimethoxycurcumin ACE2 (angiotensin converting enzyme-2) lysosome acidification SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2022.923018/full |
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