Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Foscarnet (FOS) is a pyrophosphate analogue that inhibits both cytomegalovirus (CMV) and human immunodeficiency virus (HIV) replication. We describe herein the emergence of CMV resistance to FOS in a 54-year-old man receiving FOS salvage therapy because of multidrug-resistant HIV-1 infection. Oral valganciclovir (VGCV) treatment allowed subsequently the improvement of FOS-resistant CMV infection.
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PMID:Emergence of cytomegalovirus resistance to foscarnet in a patient receiving foscarnet salvage therapy for multidrug-resistant HIV infection. 2239 36

The pyrophosphate mimic and broad spectrum antiviral phosphonoformic acid (PFA, foscarnet) was shown to freeze the pre-translocational state of the reverse transcriptase (RT) complex of the human immunodeficiency virus type 1 (HIV-1). However, PFA lacks a specificity domain, which is seen as a major reason for toxic side effects associated with the clinical use of this drug. Here, we studied the mechanism of inhibition of HIV-1 RT by the 4-chlorophenylhydrazone of mesoxalic acid (CPHM) and demonstrate that this compound also blocks RT translocation. Hot spots for inhibition with PFA or CPHM occur at template positions with a bias toward pre-translocation. Mutations at active site residue Asp-185 compromise binding of both compounds. Moreover, divalent metal ions are required for the formation of ternary complexes with either of the two compounds. However, CPHM contains both an anchor domain that likely interacts with the catalytic metal ions and a specificity domain. Thus, although the inhibitor binding sites may partly overlap, they are not identical. The K65R mutation in HIV-1 RT, which reduces affinity to PFA, increases affinity to CPHM. Details with respect to the binding sites of the two inhibitors are provided on the basis of mutagenesis studies, structure-activity relationship analyses with newly designed CPHM derivatives, and in silico docking experiments. Together, these findings validate the pre-translocated complex of HIV-1 RT as a specific target for the development of novel classes of RT inhibitors.
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PMID:Derivatives of mesoxalic acid block translocation of HIV-1 reverse transcriptase. 2535 12

Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.
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PMID:Vegetative chronic genital herpes with satisfactory response to imiquimod. 3109 Aug 30

Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.
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PMID:Vegetative chronic genital herpes with satisfactory response to imiquimod. 3326


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