Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro
Abstract The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse p...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-02-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-06104-y |
| _version_ | 1831705647886893056 |
|---|---|
| author | Devin S. M. Lewis Joanna Ho Savannah Wills Anasha Kawall Avini Sharma Krishna Chavada Maximilian C. C. J. C. Ebert Stefania Evoli Ajay Singh Srujana Rayalam Vicky Mody Shashidharamurthy Taval |
| author_facet | Devin S. M. Lewis Joanna Ho Savannah Wills Anasha Kawall Avini Sharma Krishna Chavada Maximilian C. C. J. C. Ebert Stefania Evoli Ajay Singh Srujana Rayalam Vicky Mody Shashidharamurthy Taval |
| author_sort | Devin S. M. Lewis |
| collection | DOAJ |
| description | Abstract The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 μM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus. |
| first_indexed | 2024-12-20T16:24:22Z |
| format | Article |
| id | doaj.art-b2e36b295fd24a44a89fca39420fb8d0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T16:24:22Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b2e36b295fd24a44a89fca39420fb8d02022-12-21T19:33:31ZengNature PortfolioScientific Reports2045-23222022-02-0112111110.1038/s41598-022-06104-yAloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitroDevin S. M. Lewis0Joanna Ho1Savannah Wills2Anasha Kawall3Avini Sharma4Krishna Chavada5Maximilian C. C. J. C. Ebert6Stefania Evoli7Ajay Singh8Srujana Rayalam9Vicky Mody10Shashidharamurthy Taval11Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusChemical Computing GroupChemical Computing GroupDepartment of Pharmaceutical Sciences, South University, School of PharmacyDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusDepartment of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia CampusAbstract The most common host entry point of human adapted coronaviruses (CoV) including SARS-CoV-2 is through the initial colonization in the nostril and mouth region which is responsible for spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been studied. In the present study, we have assessed in vitro enzymatic inhibitory activity of active ingredients in the oral mouth rinse products: aloin A and B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone, against two important proteases of SARS-CoV-2 PLpro and 3CLpro. Our results indicate only aloin A and B effectively inhibited proteolytic activity of PLpro with an IC50 of 13.16 and 16.08 μM. Interestingly, neither of the aloin isoforms inhibited 3CLpro enzymatic activity. Computational structural modelling of aloin A and B interaction with PLpro revealed that, both aloin isoforms form hydrogen bond with Tyr268 of PLpro, which is critical for their proteolytic activity. Furthermore, 100 ns molecular dynamics (MD) simulation studies predicted that both aloin isoforms have strong interaction with Glu167, which is required for PLpro deubiquitination activity. Our results from the in vitro deubiquitinase inhibition assay show that aloin A and B isomers exhibit deubiquitination inhibitory activity with an IC50 value of 15.68 and 17.51 µM, respectively. In conclusion, the isoforms of aloin inhibit both proteolytic and the deubiquitinating activity of SARS-CoV-2 PLpro, suggesting potential in inhibiting the replication of SARS-CoV-2 virus.https://doi.org/10.1038/s41598-022-06104-y |
| spellingShingle | Devin S. M. Lewis Joanna Ho Savannah Wills Anasha Kawall Avini Sharma Krishna Chavada Maximilian C. C. J. C. Ebert Stefania Evoli Ajay Singh Srujana Rayalam Vicky Mody Shashidharamurthy Taval Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro Scientific Reports |
| title | Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro |
| title_full | Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro |
| title_fullStr | Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro |
| title_full_unstemmed | Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro |
| title_short | Aloin isoforms (A and B) selectively inhibits proteolytic and deubiquitinating activity of papain like protease (PLpro) of SARS-CoV-2 in vitro |
| title_sort | aloin isoforms a and b selectively inhibits proteolytic and deubiquitinating activity of papain like protease plpro of sars cov 2 in vitro |
| url | https://doi.org/10.1038/s41598-022-06104-y |
| work_keys_str_mv | AT devinsmlewis aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT joannaho aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT savannahwills aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT anashakawall aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT avinisharma aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT krishnachavada aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT maximilianccjcebert aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT stefaniaevoli aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT ajaysingh aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT srujanarayalam aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT vickymody aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro AT shashidharamurthytaval aloinisoformsaandbselectivelyinhibitsproteolyticanddeubiquitinatingactivityofpapainlikeproteaseplproofsarscov2invitro |