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.