The adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus.
Bananins are a class of antiviral compounds with a unique structural signature incorporating a trioxa-adamantane moiety covalently bound to a pyridoxal derivative. Six members of this class of compounds: bananin, iodobananin, vanillinbananin, ansabananin, eubananin, and adeninobananin were synthesized and tested as inhibitors of the SARS Coronavirus (SCV) helicase. Bananin, iodobananin, vanillinbananin, and eubananin were effective inhibitors of the ATPase activity of the SCV helicase with IC50 values in the range 0.5-3 microM. A similar trend, though at slightly higher inhibitor concentrations, was observed for inhibition of the helicase activities, using a FRET-based fluorescent assay. In a cell culture system of SCV, bananin exhibited an EC50 of less than 10 microM and a CC50 of over 300 microM. Kinetics of inhibition are consistent with bananin inhibiting an intracellular process or processes involved in SCV replication.
Tanner
Julian A
JA
Department of Biochemistry, University of Hong Kong, Pokfulam, Hong Kong, China.
Zheng
Bo-Jian
BJ
Zhou
Jie
J
Watt
Rory M
RM
Jiang
Jie-Qing
JQ
Wong
Kin-Ling
KL
Lin
Yong-Ping
YP
Lu
Lin-Yu
LY
He
Ming-Liang
ML
Kung
Hsiang-Fu
HF
Kesel
Andreas J
AJ
Huang
Jian-Dong
JD
D000218:Adamantane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008253:Macaca mulatta; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; C487581:bananin; D004265:DNA Helicases; D000218:Adamantane