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Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase
As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn(2+) ion binding sites in SCV Hel thereby dis...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127030/ https://www.ncbi.nlm.nih.gov/pubmed/19233643 http://dx.doi.org/10.1016/j.bmcl.2009.02.010 |
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author | Lee, Chaewoon Lee, Jin Moo Lee, Na-Ra Jin, Bong-Suk Jang, Kyoung Jin Kim, Dong-Eun Jeong, Yong-Joo Chong, Youhoon |
author_facet | Lee, Chaewoon Lee, Jin Moo Lee, Na-Ra Jin, Bong-Suk Jang, Kyoung Jin Kim, Dong-Eun Jeong, Yong-Joo Chong, Youhoon |
author_sort | Lee, Chaewoon |
collection | PubMed |
description | As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn(2+) ion binding sites in SCV Hel thereby disrupting and inhibiting both the NTPase and helicase activities. Phosphate release assay and FRET-based assay of the ADK analogues showed that the ADKs selectively inhibit the duplex DNA-unwinding activity without significant impact on the helicase ATPase activity. Also, antiviral activities of the ADKs were shown dependent upon the substituent. Taken together, these results suggest that there might be ADK-specific binding site in the SCV Hel, which warrants further investigations with diverse ADKs to provide valuable insights into rational design of specific SCV Hel inhibitors. |
format | Online Article Text |
id | pubmed-7127030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71270302020-04-08 Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase Lee, Chaewoon Lee, Jin Moo Lee, Na-Ra Jin, Bong-Suk Jang, Kyoung Jin Kim, Dong-Eun Jeong, Yong-Joo Chong, Youhoon Bioorg Med Chem Lett Article As anti-HCV aryl diketoacids (ADK) are good metal chelators, we anticipated that ADKs might serve as potential inhibitors of SARS CoV (SCV) NTPase/helicase (Hel) by mimicking the binding modes of the bismuth complexes which effectively competes for the Zn(2+) ion binding sites in SCV Hel thereby disrupting and inhibiting both the NTPase and helicase activities. Phosphate release assay and FRET-based assay of the ADK analogues showed that the ADKs selectively inhibit the duplex DNA-unwinding activity without significant impact on the helicase ATPase activity. Also, antiviral activities of the ADKs were shown dependent upon the substituent. Taken together, these results suggest that there might be ADK-specific binding site in the SCV Hel, which warrants further investigations with diverse ADKs to provide valuable insights into rational design of specific SCV Hel inhibitors. Elsevier Ltd. 2009-03-15 2009-02-09 /pmc/articles/PMC7127030/ /pubmed/19233643 http://dx.doi.org/10.1016/j.bmcl.2009.02.010 Text en Copyright © 2009 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Lee, Chaewoon Lee, Jin Moo Lee, Na-Ra Jin, Bong-Suk Jang, Kyoung Jin Kim, Dong-Eun Jeong, Yong-Joo Chong, Youhoon Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase |
title | Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase |
title_full | Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase |
title_fullStr | Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase |
title_full_unstemmed | Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase |
title_short | Aryl diketoacids (ADK) selectively inhibit duplex DNA-unwinding activity of SARS coronavirus NTPase/helicase |
title_sort | aryl diketoacids (adk) selectively inhibit duplex dna-unwinding activity of sars coronavirus ntpase/helicase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127030/ https://www.ncbi.nlm.nih.gov/pubmed/19233643 http://dx.doi.org/10.1016/j.bmcl.2009.02.010 |
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