Towards an Effective Chemotherapy of Virus Infections: Therapeutic Potential of Cidofovir [(S)-1-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine, HPMPC] for the Treatment of DNA Virus Infections

Abstract

The acyclic nucleoside phosphonate HPMPC [(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine, cidofovir, Vistide®] has a unique profile among the antiviral agents in that it is active against a much broader spectrum of DNA viruses than any other antiviral agent, and, furthermore, shows a long-lasting antiviral activity, thus enabling infrequent dosing (for intravenous administration, as infrequent as once a week or every other week). HPMPC owes its antiviral activity to a selective inhibitory effect on viral DNA synthesis: as has been demonstrated for human cytomegalovirus (CMV), HPMPC leads to DNA chain termination following the incorporation of two consecutive HPMPC residues. The activity spectrum of HPMPC encompasses herpes-, adeno-, polyoma-, papilloma-, and poxviruses. It has been approved for the treatment of CMV retinitis in AIDS patients and has proved effective in the treatment of herpes simplex virus (HSV) infections (particularly those that are resistant to acyclovir), human papilloma virus (HPV) infections (e.g. anogenital warts and recurrent laryngeal papillomatosis) and poxvirus infections (e.g. molluscum contagiosum). It is now further explored for its therapeutic potential in the treatment of HSV, CMV and HPV infections, and various other DNA virus infections, including adenovirus infections (e.g. keratoconjunctivitis), polyomavirus infections such as PML (progressive multifocal leukoencephalopathy), poxvirus infections (e.g. molluscum contagiosum), Epstein-Barr virus (EBV)-associated infections, and human herpesvirus type 8 (HHV-8)-associated infections (e.g. Kaposi's sarcoma).