The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.

<h4>Background</h4>CR6261 was found in 2008 and F10 was found in 2009. In 2010 Friesen et al experimentally showed that Oseltamivir/Zanamivir may improve the therapeutic efficacy of CR6261. As a result, the use of CR6261 combined with a drug to provide an antibody-based therapy against a...

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Autores principales:	Wei Cui, Kui Wang, Jishou Ruan, Zhi Qi, Yi Feng, Yiming Shao, Jack A Tuszynski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8baa777a67e1441f9495d3738a25927b
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spelling	oai:doaj.org-article:8baa777a67e1441f9495d3738a25927b2021-11-18T07:16:42ZThe molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.1932-620310.1371/journal.pone.0037790https://doaj.org/article/8baa777a67e1441f9495d3738a25927b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22693576/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>CR6261 was found in 2008 and F10 was found in 2009. In 2010 Friesen et al experimentally showed that Oseltamivir/Zanamivir may improve the therapeutic efficacy of CR6261. As a result, the use of CR6261 combined with a drug to provide an antibody-based therapy against all influenza A viruses was proposed. Although CR8020 may neutralize group 2 influenza viruses and FI6 may neutralize both group 1 and group 2 influenza viruses as determined in 2011, the insight of Friesen et al is still interesting. Here, we address the following questions: how to uncover the molecular mechanism of a drug, which improves the therapeutic efficacy of mAbs and how to find drugs that enable CR6261 (CR8020, F10) to become a universal mAb.<h4>Methods and findings</h4>Using the 3D structures of 3 gbn, 3 gbm, 3 ztn, 3 ztj, 3 fku and 3 sdy, we separate the 3D structures of CR6261, F10, CR8020 and FI6, and the 3D structures of trimer HAs of H3N2 and H5N1. Based on the experimental result of Friesen et al, we have found many clues, which reveal the molecular mechanism of action for a drug and an HA-mAb complex.<h4>Conclusions</h4>Oseltamivir/Zanamivir may congruously improve the therapeutic efficacies of CR6261, F10, CR8020 and FI6 by providing an additional affinity to compensate for the loss of affinity between HA and mAb resulting from mutations. However, Oseltamivir or Zanamivir are not expected to generally widen the spectrum of these mAbs. In order to enhance CR6261, CR8020, or for F10 to become universal, we may select Azichromycin, Oseltamivir, or the combination of Azichromycin and Oseltamivir, respectively.Wei CuiKui WangJishou RuanZhi QiYi FengYiming ShaoJack A TuszynskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37790 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wei Cui Kui Wang Jishou Ruan Zhi Qi Yi Feng Yiming Shao Jack A Tuszynski The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.
description	<h4>Background</h4>CR6261 was found in 2008 and F10 was found in 2009. In 2010 Friesen et al experimentally showed that Oseltamivir/Zanamivir may improve the therapeutic efficacy of CR6261. As a result, the use of CR6261 combined with a drug to provide an antibody-based therapy against all influenza A viruses was proposed. Although CR8020 may neutralize group 2 influenza viruses and FI6 may neutralize both group 1 and group 2 influenza viruses as determined in 2011, the insight of Friesen et al is still interesting. Here, we address the following questions: how to uncover the molecular mechanism of a drug, which improves the therapeutic efficacy of mAbs and how to find drugs that enable CR6261 (CR8020, F10) to become a universal mAb.<h4>Methods and findings</h4>Using the 3D structures of 3 gbn, 3 gbm, 3 ztn, 3 ztj, 3 fku and 3 sdy, we separate the 3D structures of CR6261, F10, CR8020 and FI6, and the 3D structures of trimer HAs of H3N2 and H5N1. Based on the experimental result of Friesen et al, we have found many clues, which reveal the molecular mechanism of action for a drug and an HA-mAb complex.<h4>Conclusions</h4>Oseltamivir/Zanamivir may congruously improve the therapeutic efficacies of CR6261, F10, CR8020 and FI6 by providing an additional affinity to compensate for the loss of affinity between HA and mAb resulting from mutations. However, Oseltamivir or Zanamivir are not expected to generally widen the spectrum of these mAbs. In order to enhance CR6261, CR8020, or for F10 to become universal, we may select Azichromycin, Oseltamivir, or the combination of Azichromycin and Oseltamivir, respectively.
format	article
author	Wei Cui Kui Wang Jishou Ruan Zhi Qi Yi Feng Yiming Shao Jack A Tuszynski
author_facet	Wei Cui Kui Wang Jishou Ruan Zhi Qi Yi Feng Yiming Shao Jack A Tuszynski
author_sort	Wei Cui
title	The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.
title_short	The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.
title_full	The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.
title_fullStr	The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.
title_full_unstemmed	The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.
title_sort	molecular mechanism of action of the cr6261-azichromycin combination found through computational analysis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8baa777a67e1441f9495d3738a25927b
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The molecular mechanism of action of the CR6261-Azichromycin combination found through computational analysis.

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