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

Abstract

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 (5). 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 (5) inhibited the multiplication of influenza A virus, although influenza virus is an RNA virus that does not generate DNA.

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

“…The 1 H NMR spectra were recorded on 400 MHz and 600 MHz Brucker Advance. 13 C NMR spectra were obtained in the above instruments operating at 100.6 MHz. Melting points were obtained on an Electrothermal IA 9000 instrument (Electrothermal, Great Britain).…”

“…Brivudine is an antiviral drug used in the treatment of herpes zoster (VZV) [2,4,7]. As to antiviral activity, the literature has provided just a few examples of nucleoside analogues which are influenza A virus inhibitors [8][9][10][11][12][13]. Among approved influenza drugs (Amantadine, Rimantadine, Zanamivir, Oseltamivir, Laninamivir octanoate, Peramivir, Favipiravir and Ribavirin [4]), there is only one nucleoside analogue, namely Ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) [4,7,[14][15][16][17].…”