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)

A wide range of enveloped viruses, including human herpes simplex virus type 1, human cytomegalovirus, human T cell leukemia/lymphoma virus type I, human immunodeficiency virus type 1, Sindbis virus, and Friend erythroleukemia virus, are highly susceptible to merocyanine 540 (MC 540)-sensitized photoinactivation. By contrast, human pluripotent hematopoietic stem cells, red cells, factor VIII, and von Willebrand factor are much less sensitive. This suggests that MC 540 may be useful for the inactivation of enveloped viruses in blood and blood products. The dye has a low acute systemic toxicity, is rapidly eliminated from the blood stream, and has little or no mutagenic potential. The currently available data support the view that MC 540-sensitized photo-inactivation interferes with early events in the infectious process, notably the ability of the virus to adhere to and penetrate its host cell. The viral envelope is a major target of photodynamic damages which appear to be mediated at least in part by singlet molecular oxygen.
 ...
PMID:Merocyanine-sensitized photoinactivation of enveloped viruses. 161 87

A novel photodynamic procedure employing "preactivated" merocyanine 540 (P-MC 540) was assessed for its effectiveness in inactivating human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Merocyanine 540 was preactivated by exposure to laser light at 514 nm prior to addition to viruses or infected cells. Treatment of cell-free HIV-1 and SIV with P-MC 540 significantly reduced their ability to infect and kill MT-4 cells in vitro. Preactivated MC 540 treatment of in vitro HIV-1-infected human peripheral blood mononuclear cells also decreased viral infection as assessed by a reduction in the amounts of HIV-1 p24 antigen produced and in the number of HIV-1 antigen-positive cells. Indirect immunofluorescence assays of target cell binding showed that treatment of cell-free HIV-1 and SIV with P-MC 540 interfered with their ability to bind to CD4+ target cells. Immunoprecipitation with a monoclonal anti-CD4 antibody of P-MC 540-treated and radiolabeled HIV-1 incubated with soluble recombinant CD4 (srCD4) resulted in coprecipitation of HIV-1 viral p17 and p24 core antigens with the envelope gp120/CD4 complex, suggesting cross-linking of viral components. However, no significant decrease in the binding of treated HIV-1 to srCD4 was observed. Because of the antitumor and antiviral properties of P-MC 540, this photopreactivation procedure may represent a promising therapeutic means for controlling systemic malignancies and viral infections, and for eliminating viral contaminants in biological fluids. Unlike conventional phototherapy, this procedure does not require the delivery of light energy at the target sites following binding of the photosensitizing compounds.
 ...
PMID:Preactivated merocyanine 540 inactivates HIV-1 and SIV: potential therapeutic and blood banking applications. 173 11

Merocyanine 540 was activated by exposure to 514 nm laser light. This preactivated merocyanine 540 was then mixed (in the dark) with tumour cells, normal cells and envelope viruses to assess its antiproliferative activity. This treatment resulted in 70-90% killing of tumour cells from different cell lines while 85% of normal human peripheral blood mononuclear cells survived the treatment. However, not all types of tumour cells were affected. Preactivated merocyanine 540 was also effective in virtually completely inactivating cell-free herpes simplex and human immunodeficiency viruses. Preactivated photoactive compounds can exert their toxic effects in the dark without further dependence on light and may have potential systemic use.
 ...
PMID:Preactivation--a novel antitumour and antiviral approach. 216 76

Photoactive compounds and drugs are used therapeutically as antibacterial, antiviral and antitumor agents. This report examines the use of a photoactive compound, preactivated merocyanine 540 (pMC540), in the treatment of stomatitis in two cats that are both feline immunodeficiency virus (FIV) positive. One of the cats was also feline leukemia virus (FeLV) positive. Dramatic short term improvement is reported with the dosage regimen and complications.
 ...
PMID:Effects of preactivated MC540 in the treatment of lymphocytic plasmacytic stomatitis in feline leukemia virus and feline immunodeficiency virus positive cats. 814 94

Light-activated merocyanine 540 (pMC540) has been shown in our earlier studies to be effective against certain types of tumor cells and viruses, including human immunodeficiency virus (HIV-1). To test the potential extracorporeal and systemic use of pMC540, its toxicity was investigated in DBA/2 mice, pigs, and dogs. The lethal dose in DBA/2 mice after an i.p. injection was 370 mg/kg, and the 50% lethal dose (LD50) was 320 mg/kg; however, following i.v. administration, the lethal dose and the LD50 dose were 240 and 160 mg/kg, respectively. Tritium-labeled MC540 was used to study the biodistribution of pMC540 in DBA/2 mice. Almost 70% of the injected radioactivity was excreted within 6 h of injection. After 1 week, the pMC540 was almost completely cleared, with only 1.89% of the activity remaining, and had a plasma half-life of 23 h. Pigs injected with an accumulated dose of 10 mg/kg and followed for a period of 30 days did not show adverse signs of toxicity as monitored by SMAC-28 analysis, CBC profile, and blood-coagulation studies. A dog injected with a single dose of 20 mg/kg showed induction of the hepatic enzymes glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (AST); however, serum levels of gamma-glutamyl transpeptidase (GGT) remained unchanged. The data presented herein may serve to identify certain drug-dose limitations in the systemic use of pMC540.
 ...
PMID:Biodistribution and toxicity of photoproducts of merocyanine 540. 845 86

Using the water-soluble naphthalene carrier of singlet oxygen NDPO2, we have shown that pure singlet oxygen is able to inactivate enveloped viruses (human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus, vesicular stomatitis virus), but has no effect on non-enveloped viruses (adenovirus and poliovirus 1). These results are related to the experiments on photoinactivation of viruses by hydrophobic photosensitizers (merocyanine 540, hypericin, phthalocyanines, hematoporphyrin and benzoporphyrin derivatives) and they strengthen the hypothesis that singlet oxygen plays a predominant role in this process.
 ...
PMID:Virucidal activity of pure singlet oxygen generated by thermolysis of a water-soluble naphthalene endoperoxide. 898 9