Cytomegalovirus (CMV) is a genus of Herpesvirales. Several species of CMV have been identified and classified for different mammals, including human CMV (HCMV), chimpanzee CMV (CCMV), mouse CMV (MCMV), guinea pig CMV (GPCMV) and so on. It can cause neuroinvasive infections in immunocompromised patients. Cidofovir (HPMPC) has been proven to be effective in a variety of experimental herpes virus infections including cutaneous, systemic and genital herpes simplex disease, but its use is limited by nephrotoxicity.
Cyclic HPMPC is a potent antiviral agent. It is the cyclic congener of HPMPC, which is significantly less nephrotoxic than HPMPC in kinds of animal species. This drug displays similar in vitro activity to the parent compound HPMPC against various herpesviruses, including herpes simplex virus (HSV) and HCMV.
Cyclic HPMPC is safe and effective against GPCMV infection in immunodeficient animals.
Cyclic HPMPC (5 mg/kg/day; IP, for 7 days) has no adverse effects on white blood cell counts and exhibits no toxicity in either liver or kidney; all of the cyclic HPMPC treated guinea pigs are survived with no visible signs of toxicity.
Cyclic HPMPC (35 mg/kg; IP, single dosage) improves the infant survival rate from 28.2% (11/39) to 83.7% (36/43) (P < 0.001) in pregnant Hartley guinea pigs which are inoculated with GPCMV; and also extends the duration of pregnancy. Cyclic HPMPC can not prevent virus infection of the placenta or vertical transmission of the mother or baby animals, but significantly decreases the amount of GPCMV in tissues.
Besides, Cyclic HPMPC has inhibitory activity against orthopoxvirus replication with EC50s of 50.6 μM for vaccinia virus in human foreskin fibroblast (HFF) cells.
In conclusion, cyclic HPMPC is a potent antiviral agent for various herpesviruses and orthopoxvirus, exhibiting less nephrotoxic than its parent compound HPMPC.