carbocyclic-3-deazaadenosine and pyrazofurin

Various nucleoside analogues, selected on the basis of their previously established broad-spectrum antiviral properties, were evaluated for their potency and selectivity as inhibitors of the in vitro replication of the iridovirus, African swine fever virus (ASFV). The test compounds included (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine, (RS)-3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, (S)-9-(2,3-dihydroxypropyl)adenine, carbocyclic 3-deazaadenosine (C-c3Ado), 3'-azido-2',3'-dideoxythymidine, pyrazofurin and ribavirin. As the most efficacious inhibitors of ASFV replication emerged (S)-HPMPA followed by C-c3Ado. The minimum inhibitory concentration of (S)-HPMPA for ASFV replication was 0.01 microgram/ml, and its selectivity index was 15,000. The corresponding values for C-c3Ado were 0.025 micrograms/ml and 8000, respectively. It would seem justified to further pursue these compounds for their anti ASFV activity in vivo.

Topics: Adenine; African Swine Fever Virus; Amides; Animals; Antiviral Agents; Dose-Response Relationship, Drug; Iridoviridae; Organophosphonates; Organophosphorus Compounds; Pyrazoles; Ribavirin; Ribonucleosides; Ribose; Thymidine; Tubercidin; Vero Cells; Virus Replication; Zidovudine

Several nucleoside analogues which have previously been established as broad-spectrum antiviral agents, i.e. ribavirin, vidarabine, pyrazofurin, tubercidin, carbodine, (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], carbocyclic 3-deazaadenosine (C-c3 Ado), (RS)-3-adenine-9-yl-2-hydroxypropanoic acid [(RS)-AHPA] isobutyl ester and neplanocin A were compared for their potency and selectivity as inhibitors of human rotavirus (strains Wa, KUN and MO) replication in vitro. As the most efficacious inhibitors emerged (S)-DHPA, C-c3 Ado, (RS)-AHPA isobutyl ester and neplanocin A, with a minimum inhibitory concentration of 60, 1.4, 1.2 and 0.2 micrograms/ml, and a selectivity index of greater than 3, 70, 80 and greater than 20, respectively. As has been postulated for their antiviral action in general, these adenosine analogues probably owe their anti-rotavirus activity to inhibition of S-adenosylhomocysteine hydrolase, a key enzyme in regulating methylations including those that are required for the maturation of viral mRNA.

Topics: Adenine; Adenosine; Amides; Antiviral Agents; Cell Line; Cytidine; Dose-Response Relationship, Drug; Pyrazoles; Ribavirin; Ribonucleosides; Ribose; Rotavirus; Tubercidin; Vidarabine; Virus Replication