Synergistic effect of zanamivir-porphyrin conjugates on inhibition of neuraminidase and inactivation of influenza virus.
New anti-influenza agents of tetravalent zanamivir on a porphyrin scaffold were synthesized. These compounds are 10 to 100 times more potent in inhibiting influenza replications even though they are somewhat less potent in neuraminidase inhibition than the monomeric zanamivir. The enhanced anti-influenza activity is probably attributable to the additional viral inactivation by singlet oxygen due to sensitization of the porphyrin moiety, which is brought in close proximity of virus by the conjugated zanamivir in a manner resembling the "magic bullet" mechanism.
Wen
Wen-Hsien
WH
Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan.
Lin
Mengi
M
Su
Ching-Yao
CY
Wang
Shi-Yun
SY
Cheng
Yih-Shyun E
YS
Fang
Jim-Min
JM
Wong
Chi-Huey
CH
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000502:physiology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D053243:Zanamivir / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011166:Porphyrins; D009439:Neuraminidase; D053243:Zanamivir