Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup>
A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides...
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MDPI AG
2022-12-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/12/786 |
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| author | D. P. Nagahawatta N. M. Liyanage Jun-Geon Je H. H. A. C. K. Jayawardhana Thilina U. Jayawardena Seong-Hun Jeong Hyung-Jun Kwon Cheol Soo Choi You-Jin Jeon |
| author_facet | D. P. Nagahawatta N. M. Liyanage Jun-Geon Je H. H. A. C. K. Jayawardhana Thilina U. Jayawardena Seong-Hun Jeong Hyung-Jun Kwon Cheol Soo Choi You-Jin Jeon |
| author_sort | D. P. Nagahawatta |
| collection | DOAJ |
| description | A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PL<sup>pro</sup>) and 3-chymotrypsin-like protease (3CL<sup>pro</sup>) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PL<sup>pro</sup> is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CL<sup>pro</sup> and PL<sup>pro</sup> of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CL<sup>pro</sup> and PL<sup>pro</sup> using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CL<sup>pro</sup> and PL<sup>pro</sup> structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CL<sup>pro</sup> and PL<sup>pro</sup> of SARS-CoV-2. |
| first_indexed | 2024-03-09T16:10:30Z |
| format | Article |
| id | doaj.art-e8308f08eda74ecf94964def42ed0058 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T16:10:30Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-e8308f08eda74ecf94964def42ed00582023-11-24T16:20:10ZengMDPI AGMarine Drugs1660-33972022-12-01201278610.3390/md20120786Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup>D. P. Nagahawatta0N. M. Liyanage1Jun-Geon Je2H. H. A. C. K. Jayawardhana3Thilina U. Jayawardena4Seong-Hun Jeong5Hyung-Jun Kwon6Cheol Soo Choi7You-Jin Jeon8Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of KoreaDepartment of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of KoreaDepartment of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of KoreaDepartment of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of KoreaDepartment of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières, Trois-Rivières, QC G8Z 4M3, CanadaFunctional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 56212, Republic of KoreaFunctional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 56212, Republic of KoreaKorea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of KoreaDepartment of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of KoreaA global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PL<sup>pro</sup>) and 3-chymotrypsin-like protease (3CL<sup>pro</sup>) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PL<sup>pro</sup> is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CL<sup>pro</sup> and PL<sup>pro</sup> of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CL<sup>pro</sup> and PL<sup>pro</sup> using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CL<sup>pro</sup> and PL<sup>pro</sup> structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CL<sup>pro</sup> and PL<sup>pro</sup> of SARS-CoV-2.https://www.mdpi.com/1660-3397/20/12/786SARS-CoV-23CL<sup>pro</sup>PL<sup>pro</sup>marine natural productmolecular dockingmulti-target approach |
| spellingShingle | D. P. Nagahawatta N. M. Liyanage Jun-Geon Je H. H. A. C. K. Jayawardhana Thilina U. Jayawardena Seong-Hun Jeong Hyung-Jun Kwon Cheol Soo Choi You-Jin Jeon Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup> Marine Drugs SARS-CoV-2 3CL<sup>pro</sup> PL<sup>pro</sup> marine natural product molecular docking multi-target approach |
| title | Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup> |
| title_full | Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup> |
| title_fullStr | Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup> |
| title_full_unstemmed | Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup> |
| title_short | Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CL<sup>pro</sup> and PL<sup>pro</sup> |
| title_sort | polyphenolic compounds isolated from marine algae attenuate the replication of sars cov 2 in the host cell through a multi target approach of 3cl sup pro sup and pl sup pro sup |
| topic | SARS-CoV-2 3CL<sup>pro</sup> PL<sup>pro</sup> marine natural product molecular docking multi-target approach |
| url | https://www.mdpi.com/1660-3397/20/12/786 |
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