<i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies
In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/19/5844 |
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| author | Heba A. El Gizawy Sylvia A. Boshra Ahmed Mostafa Sara H. Mahmoud Muhammad I. Ismail Aisha A. Alsfouk Azza T. Taher Ahmed A. Al-Karmalawy |
| author_facet | Heba A. El Gizawy Sylvia A. Boshra Ahmed Mostafa Sara H. Mahmoud Muhammad I. Ismail Aisha A. Alsfouk Azza T. Taher Ahmed A. Al-Karmalawy |
| author_sort | Heba A. El Gizawy |
| collection | DOAJ |
| description | In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid <b>1</b>, rutin <b>2</b>, gallic acid <b>3</b>, and chlorogenic acid <b>4</b> were isolated from the leaves of <i>Pimenta dioica</i> (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (<b>1</b>–<b>4</b>) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC<sub>50</sub>) and SARS-CoV-2 inhibitory concentrations (IC<sub>50</sub>). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with <i>P. dioca</i> aqueous extract, ferulic acid <b>1</b>, rutin <b>2</b>, gallic acid <b>3</b>, and chlorogenic acid <b>4</b> were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin <b>2</b>, gallic acid <b>3</b>, and chlorogenic acid <b>4</b> showed remarkable anti-SARS-CoV-2 activities with IC<sub>50</sub> values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid <b>1</b> and rutin <b>2</b> treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin <b>2</b> either alone or in combination with other isolates for COVID-19 management. |
| first_indexed | 2024-03-10T06:54:59Z |
| format | Article |
| id | doaj.art-65c0ca7bb5ca438db93d0a5f1f6cb2c6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T06:54:59Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-65c0ca7bb5ca438db93d0a5f1f6cb2c62023-11-22T16:33:29ZengMDPI AGMolecules1420-30492021-09-012619584410.3390/molecules26195844<i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo StudiesHeba A. El Gizawy0Sylvia A. Boshra1Ahmed Mostafa2Sara H. Mahmoud3Muhammad I. Ismail4Aisha A. Alsfouk5Azza T. Taher6Ahmed A. Al-Karmalawy7Department of Pharmacognosy, Faculty of Pharmacy, October 6 University (O6U), October 6 City, Giza 12585, EgyptDepartment of Biochemistry, Faculty of Pharmacy, October 6 University (O6U), October 6 City, Giza 12585, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, Al-Sherouk City, Cairo-Suez Desert Road, Cairo 11837, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi ArabiaDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, EgyptDepartment of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Horus University-Egypt, New Damietta 34518, EgyptIn response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid <b>1</b>, rutin <b>2</b>, gallic acid <b>3</b>, and chlorogenic acid <b>4</b> were isolated from the leaves of <i>Pimenta dioica</i> (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (<b>1</b>–<b>4</b>) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC<sub>50</sub>) and SARS-CoV-2 inhibitory concentrations (IC<sub>50</sub>). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with <i>P. dioca</i> aqueous extract, ferulic acid <b>1</b>, rutin <b>2</b>, gallic acid <b>3</b>, and chlorogenic acid <b>4</b> were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin <b>2</b>, gallic acid <b>3</b>, and chlorogenic acid <b>4</b> showed remarkable anti-SARS-CoV-2 activities with IC<sub>50</sub> values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid <b>1</b> and rutin <b>2</b> treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin <b>2</b> either alone or in combination with other isolates for COVID-19 management.https://www.mdpi.com/1420-3049/26/19/5844<i>Pimenta</i>rutinanti-SARS-CoV-2docking and dynamics simulationsin vitro and in vivo studies |
| spellingShingle | Heba A. El Gizawy Sylvia A. Boshra Ahmed Mostafa Sara H. Mahmoud Muhammad I. Ismail Aisha A. Alsfouk Azza T. Taher Ahmed A. Al-Karmalawy <i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies Molecules <i>Pimenta</i> rutin anti-SARS-CoV-2 docking and dynamics simulations in vitro and in vivo studies |
| title | <i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies |
| title_full | <i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies |
| title_fullStr | <i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies |
| title_full_unstemmed | <i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies |
| title_short | <i>Pimenta dioica</i> (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies |
| title_sort | i pimenta dioica i l merr bioactive constituents exert anti sars cov 2 and anti inflammatory activities molecular docking and dynamics in vitro and in vivo studies |
| topic | <i>Pimenta</i> rutin anti-SARS-CoV-2 docking and dynamics simulations in vitro and in vivo studies |
| url | https://www.mdpi.com/1420-3049/26/19/5844 |
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