Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor

Influenza A viruses leading to infectious respiratory diseases cause seasonal epidemics and sometimes periodic global pandemics. Viral polymerase is an attractive target in inhibiting viral replication, and 4′-ethynyladenosine, which has been reported as a highly potent anti-human immunode...

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Main Authors:	Toshifumi Takeuchi, Nongluk Sriwilaijaroen, Ayako Sakuraba, Ei Hayashi, Shinji Kamisuki, Yasuo Suzuki, Hiroshi Ohrui, Fumio Sugawara
Format:	Article
Language:	English
Published:	MDPI AG 2019-07-01
Series:	Molecules
Subjects:	4′-ethynyl-2′-deoxyadenosine 5′-monophosphate influenza anti-influenza activity
Online Access:	https://www.mdpi.com/1420-3049/24/14/2603

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spelling	doaj-3e6d63a673c942bea6e042a659755d602020-11-25T01:42:51ZengMDPI AGMolecules1420-30492019-07-012414260310.3390/molecules24142603molecules24142603Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a InhibitorToshifumi Takeuchi0Nongluk Sriwilaijaroen1Ayako Sakuraba2Ei Hayashi3Shinji Kamisuki4Yasuo Suzuki5Hiroshi Ohrui6Fumio Sugawara7Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Preclinical Sciences, Faculty of Medicine, Thammasat University, Pathumthani 12120, ThailandDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanSchool of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, JapanHealth Science Hills, College of Life and Health Sciences, Chubu University, Kasugai, Aichi 487-8501, JapanYokohama University of Pharmacy, Matano-cho 601, Totsuka-ku, Yokohama, Kanagawa 245-0066, JapanDepartment of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanInfluenza A viruses leading to infectious respiratory diseases cause seasonal epidemics and sometimes periodic global pandemics. Viral polymerase is an attractive target in inhibiting viral replication, and 4′-ethynyladenosine, which has been reported as a highly potent anti-human immunodeficiency virus (HIV) nucleoside derivative, can work as an anti-influenza agent. Herein, we designed and synthesized a 4′-ethynyl-2′-deoxyadenosine 5′-monophosphate analog called EdAP (<b>5</b>). EdAP exhibited potent inhibition against influenza virus multiplication in Madin−Darby canine kidney (MDCK) cells transfected with human α2-6-sialyltransferase (SIAT1) cDNA and did not show any toxicity toward the cells. Surprisingly, this DNA-type nucleic acid analog (<b>5</b>) inhibited the multiplication of influenza A virus, although influenza virus is an RNA virus that does not generate DNA.https://www.mdpi.com/1420-3049/24/14/26034′-ethynyl-2′-deoxyadenosine 5′-monophosphateinfluenzaanti-influenza activity
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Toshifumi Takeuchi Nongluk Sriwilaijaroen Ayako Sakuraba Ei Hayashi Shinji Kamisuki Yasuo Suzuki Hiroshi Ohrui Fumio Sugawara
spellingShingle	Toshifumi Takeuchi Nongluk Sriwilaijaroen Ayako Sakuraba Ei Hayashi Shinji Kamisuki Yasuo Suzuki Hiroshi Ohrui Fumio Sugawara Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor Molecules 4′-ethynyl-2′-deoxyadenosine 5′-monophosphate influenza anti-influenza activity
author_facet	Toshifumi Takeuchi Nongluk Sriwilaijaroen Ayako Sakuraba Ei Hayashi Shinji Kamisuki Yasuo Suzuki Hiroshi Ohrui Fumio Sugawara
author_sort	Toshifumi Takeuchi
title	Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor
title_short	Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor
title_full	Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor
title_fullStr	Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor
title_full_unstemmed	Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor
title_sort	design, synthesis, and biological evaluation of edap, a 4′-ethynyl-2′-deoxyadenosine 5′-monophosphate analog, as a potent influenza a inhibitor
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-07-01
description	Influenza A viruses leading to infectious respiratory diseases cause seasonal epidemics and sometimes periodic global pandemics. Viral polymerase is an attractive target in inhibiting viral replication, and 4′-ethynyladenosine, which has been reported as a highly potent anti-human immunodeficiency virus (HIV) nucleoside derivative, can work as an anti-influenza agent. Herein, we designed and synthesized a 4′-ethynyl-2′-deoxyadenosine 5′-monophosphate analog called EdAP (<b>5</b>). EdAP exhibited potent inhibition against influenza virus multiplication in Madin−Darby canine kidney (MDCK) cells transfected with human α2-6-sialyltransferase (SIAT1) cDNA and did not show any toxicity toward the cells. Surprisingly, this DNA-type nucleic acid analog (<b>5</b>) inhibited the multiplication of influenza A virus, although influenza virus is an RNA virus that does not generate DNA.
topic	4′-ethynyl-2′-deoxyadenosine 5′-monophosphate influenza anti-influenza activity
url	https://www.mdpi.com/1420-3049/24/14/2603
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Design, Synthesis, and Biological Evaluation of EdAP, a 4′-Ethynyl-2′-Deoxyadenosine 5′-Monophosphate Analog, as a Potent Influenza a Inhibitor

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