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

• 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
• ISSN: 1420-3049

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&#8242;-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&#8242;-ethynyl-2&#8242;-deoxyadenosine 5&#8242;-monophosphate analog called EdAP (<b>5</b>). EdAP exhibited potent inhibition against influenza virus multiplication in Madin&#8722;Darby canine kidney (MDCK) cells transfected with human &#945;2-6-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.