1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since 2020. The nucleocapsid (N) protein plays a crucial role in the life cycle of SARS-CoV-2. Here, we established a method to screen inhibitors of N protein by using microscale thermophoresis assays to obtain potentia...
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Compuscript Ltd
2023-07-01
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Series: | Acta Materia Medica |
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Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0021 |
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author | Yang Liu Kuiru Sa Wei Xu Yongkang Chen Jing Liang Peng Zou Lixia Chen |
author_facet | Yang Liu Kuiru Sa Wei Xu Yongkang Chen Jing Liang Peng Zou Lixia Chen |
author_sort | Yang Liu |
collection | DOAJ |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since 2020. The nucleocapsid (N) protein plays a crucial role in the life cycle of SARS-CoV-2. Here, we established a method to screen inhibitors of N protein by using microscale thermophoresis assays to obtain potential anti-SARS-CoV-2 agents. We identified 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (N-17, a diphenylheptane) as a compound with outstanding inhibitory activity. We further validated the binding of N-17 to the N-terminal domain of N protein (N-NTD) by using drug affinity responsive target stability assays. We evaluated the ability of N-17 to bind N protein and predicted the affinity of N-17 to the N-NTD with molecular docking and molecular dynamics simulation. N-17 exhibited excellent anti-viral activity against HCoV-OC43 and SARS-CoV-2, with EC50 values of 0.16 ± 0.01 μM and 0.17 ± 0.07 μM, respectively. Thus, we discovered a novel SARS-CoV-2 inhibitor targeting the N protein and validated its anti-viral activity in vitro. Our results may contribute to the development of promising therapeutic agents for COVID-19. |
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id | doaj.art-608f498668194e6ea240184f8f91733f |
institution | Directory Open Access Journal |
issn | 2737-7946 |
language | English |
last_indexed | 2024-03-11T18:58:24Z |
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series | Acta Materia Medica |
spelling | doaj.art-608f498668194e6ea240184f8f91733f2023-10-10T13:47:19ZengCompuscript LtdActa Materia Medica2737-79462023-07-012327028010.15212/AMM-2023-00211,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid proteinYang Liu0Kuiru Sa1Wei Xu2Yongkang Chen3Jing Liang4Peng Zou5Lixia Chen6Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, ChinaWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaWuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since 2020. The nucleocapsid (N) protein plays a crucial role in the life cycle of SARS-CoV-2. Here, we established a method to screen inhibitors of N protein by using microscale thermophoresis assays to obtain potential anti-SARS-CoV-2 agents. We identified 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (N-17, a diphenylheptane) as a compound with outstanding inhibitory activity. We further validated the binding of N-17 to the N-terminal domain of N protein (N-NTD) by using drug affinity responsive target stability assays. We evaluated the ability of N-17 to bind N protein and predicted the affinity of N-17 to the N-NTD with molecular docking and molecular dynamics simulation. N-17 exhibited excellent anti-viral activity against HCoV-OC43 and SARS-CoV-2, with EC50 values of 0.16 ± 0.01 μM and 0.17 ± 0.07 μM, respectively. Thus, we discovered a novel SARS-CoV-2 inhibitor targeting the N protein and validated its anti-viral activity in vitro. Our results may contribute to the development of promising therapeutic agents for COVID-19.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0021sars-cov-2anti-viraln-ntd inhibitor |
spellingShingle | Yang Liu Kuiru Sa Wei Xu Yongkang Chen Jing Liang Peng Zou Lixia Chen 1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein Acta Materia Medica sars-cov-2 anti-viral n-ntd inhibitor |
title | 1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein |
title_full | 1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein |
title_fullStr | 1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein |
title_full_unstemmed | 1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein |
title_short | 1,7-Bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one inhibits SARS-CoV-2 by targeting the nucleocapsid protein |
title_sort | 1 7 bis 4 hydroxyphenyl 1 4 6 heptatrien 3 one inhibits sars cov 2 by targeting the nucleocapsid protein |
topic | sars-cov-2 anti-viral n-ntd inhibitor |
url | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0021 |
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