Recent advances in neuraminidase inhibitor development as anti-influenza drugs.
The recent emergence of the highly pathogenic H5N1 subtype of avian influenza virus (AIV) and of the new type of human influenza A (H1N1) have emphasized the need for the development of effective anti-influenza drugs. Presently, neuraminidase (NA) inhibitors are widely used in the treatment and prophylaxis of human influenza virus infection, and tremendous efforts have been made to develop more potent NA inhibitors to combat resistance and new influenza viruses. In this review, we discuss the structural characteristics of NA catalytic domains and the recent developments of new NA inhibitors using structure-based drug design strategies. These drugs include analogues of zanamivir, analogues of oseltamivir, analogues of peramivir, and analogues of aromatic carboxylic acid and present promising options for therapeutics or leads for further development of NA inhibitors that may be useful in the event of a future influenza pandemic.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Graduate School of the Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
Enguang
E
Feng
Deju
D
Ye
Jian
J
Li
Dengyou
D
Zhang
Jinfang
J
Wang
Fei
F
Zhao
Rolf
R
Hilgenfeld
Mingyue
M
Zheng
Hualiang
H
Jiang
Hong
H
Liu
D000146:Acids, Carbocyclic; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D019817:Benzoic Acid / Q000737:chemistry / Q000494:pharmacology; D003517:Cyclopentanes / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000201:enzymology; D007251:Influenza, Human / Q000188:drug therapy; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009975:Orthomyxoviridae / Q000187:drug effects / Q000201:enzymology*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D053139:Oseltamivir / Q000737:chemistry / Q000494:pharmacology; D053243:Zanamivir / Q000737:chemistry / Q000494:pharmacology
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D053139:Oseltamivir; D019817:Benzoic Acid; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir