Abstract
Cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC] is an acyclic nucleoside analog approved since 1996 for clinical use in the treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Cidofovir (CDV) has broad-spectrum activity against DNA viruses, including herpes-, adeno-, polyoma-, papilloma- and poxviruses. Among poxviruses, cidofovir has shown in vitro activity against orthopox [vaccinia, variola (smallpox), cowpox, monkeypox, camelpox, ectromelia], molluscipox [molluscum contagiosum] and parapox [orf] viruses. The anti-poxvirus activity of cidofovir in vivo has been shown in different models of infection when the compound was administered either intraperitoneal, intranasal (aerosolized) or topically. In humans, cidofovir has been successfully used for the treatment of recalcitrant molluscum contagiosum virus and orf virus in immunocompromised patients. CDV remains a reference compound against poxviruses and holds potential for the therapy and short-term prophylaxis of not only orthopox- but also parapox- and molluscipoxvirus infections.
Highlights
The antiviral activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC, cidofovir, CDV) (Figure 1) against human cytomegalovirus (HCMV) and other DNA viruses was firstViruses 2010, 2 reported in 1986 [1]
In 1996, the intravenous form of CDV was licensed for clinical use, under the trade name of Vistide®, for the systemic treatment of HCMV retinitis in AIDS patients
CDV is a close congener of HPMPA [(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine], which was the first acyclic nucleoside phosphonate (ANP) described with broad spectrum anti-DNA
Summary
The antiviral activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC, cidofovir, CDV) (Figure 1) against human cytomegalovirus (HCMV) and other DNA viruses was first. CDV is a close congener of HPMPA [(S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine], which was the first acyclic nucleoside phosphonate (ANP) described with broad spectrum anti-DNA virus activity [1,2]. The discovery of ANPs represented a breakthrough in the treatment of DNA viruses and retroviruses According to their activity spectrum, the first generation of ANPs can be classified in three categories: (i) the “HPMP” (i.e., 3-hydroxy-2-phosphonylmethoxypropyl) derivatives, represented by HPMPC (cidofovir, CDV), which displays activity against a broad variety of DNA viruses, (ii) the “PME” (i.e., 2-phosphonylmethoxyethyl) derivatives with activity against DNA viruses. Retroviruses, and iii) the “PMP” (i.e., 2-phosphonylmethoxypropyl) derivatives, represented by, respectively, PMEA (adefovir) and PMPA (tenofovir) These three representative compounds have been licensed for the treatment of HCMV retinitis in AIDS patients (CDV, Vistide®), chronic hepatitis. 5-azacytosine analog of CDV, 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [6,7]
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