Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor
Despite the recent development of RNA replication-targeted COVID-19 drugs by global pharmaceutical companies, their prescription in clinical practice is limited by certain factors, including drug interaction, reproductive toxicity, and drug resistance. COVID-19 drugs with multiple targets for the SA...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/19/4170 |
| _version_ | 1797477498647216128 |
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| author | Young Soo Kim Buyun Kim Eun-Bin Kwon Hwan-Suck Chung Jang-Gi Choi |
| author_facet | Young Soo Kim Buyun Kim Eun-Bin Kwon Hwan-Suck Chung Jang-Gi Choi |
| author_sort | Young Soo Kim |
| collection | DOAJ |
| description | Despite the recent development of RNA replication-targeted COVID-19 drugs by global pharmaceutical companies, their prescription in clinical practice is limited by certain factors, including drug interaction, reproductive toxicity, and drug resistance. COVID-19 drugs with multiple targets for the SARS-CoV-2 life cycle may lead to a successful reduction in drug resistance as well as enhanced therapeutic efficacy, and natural products are a potential source of molecules with therapeutic effects against COVID-19. In this study, we investigated the inhibitory efficacy of mulberrofuran G (MG), a component of <i>Morus alba</i> L., also known as mulberry, which has been used as food and traditional medicine, on the binding of the spike S1 receptor-binding domain (RBD) protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is the initial stage of the SARS-CoV-2 infection. In competitive enzyme-linked immunosorbent assays, MG effectively blocked the spike S1 RBD: ACE2 receptor molecular binding, and investigations using the BLItz system and in silico modeling revealed that MG has high affinity for both proteins. Finally, we confirmed that MG inhibits the entry of SARS-CoV-2 spike pseudotyped virus and a clinical isolate of SARS-CoV-2 into cells, suggesting that MG might be a promising therapeutic candidate for preventing SARS-CoV-2 binding to the cell surface during early infection. |
| first_indexed | 2024-03-09T21:18:31Z |
| format | Article |
| id | doaj.art-1544af4355cc4a7ea2289b7a6b2fd5f5 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T21:18:31Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-1544af4355cc4a7ea2289b7a6b2fd5f52023-11-23T21:26:48ZengMDPI AGNutrients2072-66432022-10-011419417010.3390/nu14194170Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 ReceptorYoung Soo Kim0Buyun Kim1Eun-Bin Kwon2Hwan-Suck Chung3Jang-Gi Choi4Korean Medicine Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 41062, KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 41062, KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 41062, KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 41062, KoreaKorean Medicine Application Center, Korea Institute of Oriental Medicine, Dong-gu, Daegu 41062, KoreaDespite the recent development of RNA replication-targeted COVID-19 drugs by global pharmaceutical companies, their prescription in clinical practice is limited by certain factors, including drug interaction, reproductive toxicity, and drug resistance. COVID-19 drugs with multiple targets for the SARS-CoV-2 life cycle may lead to a successful reduction in drug resistance as well as enhanced therapeutic efficacy, and natural products are a potential source of molecules with therapeutic effects against COVID-19. In this study, we investigated the inhibitory efficacy of mulberrofuran G (MG), a component of <i>Morus alba</i> L., also known as mulberry, which has been used as food and traditional medicine, on the binding of the spike S1 receptor-binding domain (RBD) protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is the initial stage of the SARS-CoV-2 infection. In competitive enzyme-linked immunosorbent assays, MG effectively blocked the spike S1 RBD: ACE2 receptor molecular binding, and investigations using the BLItz system and in silico modeling revealed that MG has high affinity for both proteins. Finally, we confirmed that MG inhibits the entry of SARS-CoV-2 spike pseudotyped virus and a clinical isolate of SARS-CoV-2 into cells, suggesting that MG might be a promising therapeutic candidate for preventing SARS-CoV-2 binding to the cell surface during early infection.https://www.mdpi.com/2072-6643/14/19/4170coronavirus disease 2019severe acute respiratory syndrome coronavirus 2mulberrymulberrofuran Gspike proteinACE2 receptor |
| spellingShingle | Young Soo Kim Buyun Kim Eun-Bin Kwon Hwan-Suck Chung Jang-Gi Choi Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor Nutrients coronavirus disease 2019 severe acute respiratory syndrome coronavirus 2 mulberry mulberrofuran G spike protein ACE2 receptor |
| title | Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor |
| title_full | Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor |
| title_fullStr | Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor |
| title_full_unstemmed | Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor |
| title_short | Mulberrofuran G, a Mulberry Component, Prevents SARS-CoV-2 Infection by Blocking the Interaction between SARS-CoV-2 Spike Protein S1 Receptor-Binding Domain and Human Angiotensin-Converting Enzyme 2 Receptor |
| title_sort | mulberrofuran g a mulberry component prevents sars cov 2 infection by blocking the interaction between sars cov 2 spike protein s1 receptor binding domain and human angiotensin converting enzyme 2 receptor |
| topic | coronavirus disease 2019 severe acute respiratory syndrome coronavirus 2 mulberry mulberrofuran G spike protein ACE2 receptor |
| url | https://www.mdpi.com/2072-6643/14/19/4170 |
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