Broad-Spectrum Antiviral Activities ofNeplanocin A, 3-Deazaneplanocin A,andTheir 5'-Nor Derivatives

(DHCDA),allpotent inhibitors ofS-adenosylhomocysteine (AdoHcy) hydrolase, were studied fortheir broad-spectrum antiviral potential. 3-Deazaneplanocin A,DHCA,andDHCDA provedspecifically effective against vesicular stomatitis virus, vaccinia virus, parainfluenza virus, reovirus, androtavirus. Theirselectivity was greater thanthatof neplanocin A,particularly against vesicular stomatitis virusandrotavirus. As couldbeexpected from adenosine analogs that aredirectly targeted atAdoHcyhydrolase, 3-deazaneplanocin A,DHCA,andDHCDA werefully active inadenosine kinase-deficient cells, implying thattheir activity didnotdepend on phosphorylation byadenosine kinase. NoneoftheAdoHcyhydrolase inhibitors showedselective activity against human immunodeficiency virus (type 1).3-Deazaneplanocin A ata doseof0.5mg/kgper dayconferred marked protection against a lethal infection ofnewbornmicewithvesicular stomatitis virus. Neplanocin A isapotent antiviral agentactive against a broadspectrum ofviruses belonging tothePoxviridae, Rhabdoviridae, Paramyxoviridae, andReoviridae (6). Itis particularly effective against vaccinia virus, vesicular stomatitis virus, parainfluenza virus, measles virus, reovirus (6), andhumanrotavirus (20). Neplanocin A isapotent inhibitor ofS-adenosylhomocysteine