Activity of several S-adenosylhomocysteine hydrolase inhibitors against African swine fever virus replication in Vero cells.
Several inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase have been found to selectively suppress the replication of African swine fever virus (ASFV) in Vero cells. Of the compounds tested, 3-deazaneplanocin A proved to be the most potent and selective inhibitor of ASFV replication. Its selectivity index (SI) was 3000. Then followed 9-(trans-2',trans-3'-dihydroxycyclopentyl)-3- deazaadenine (SI = 2500), the 4'beta-vinyl derivative of 9-(trans-2',trans-3'-dihydroxycyclopentyl)adenine (SI = 2000), 6'beta-fluoroaristeromycin (SI = 1250), 4',5'-unsaturated 5'-fluoroadenosine (MDL 28842) and 9-(trans-2',trans-3'-dihydroxycyclopentyl)adenine (SI = 667), 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine and the 4 beta-methyl derivative of 9-(trans-2',trans-3'- dihydroxycyclopentyl)adenine (SI = 400), 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (SI = 200). We postulate that the mechanism of anti-ASFV action of these compounds is based on the inhibition of AdoHcy hydrolase, thus resulting in the accumulation of AdoHcy and suppression of methylation reactions needed for viral mRNA maturation.
Villalón
M D
MD
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Gil-Fernández
C
C
De Clercq
E
E
D043383:Adenosylhomocysteinase; D000358:African Swine Fever Virus / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D012367:RNA, Viral / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014709:Vero Cells; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D012367:RNA, Viral; D006867:Hydrolases; D043383:Adenosylhomocysteinase