In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate

• Published in: Virology journal Vol. 12; no. 1; p. 132
• Main Authors: Styczynski, Ashley R, Anwar, Khandaker N, Sultana, Habiba, Ghanem, Abdelhamid, Lurain, Nell, Chua, Aishi, Ghassemi, Mahmood, Novak, Richard M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30-08-2015; BioMed Central
• Subjects: Administration, Intravaginal; Analysis; Animals; Anti-Infective Agents, Local - adverse effects; Anti-Infective Agents, Local - pharmacology; Antiviral agents; Cell Survival - drug effects; Cells, Cultured; Complications and side effects; Copper compounds; Disease Transmission, Infectious - prevention & control; Dosage and administration; Dose-Response Relationship, Drug; Female; Health aspects; HIV (Viruses); HIV infection; HIV Infections - prevention & control; HIV Infections - transmission; Humans; Indoles - adverse effects; Indoles - pharmacology; Infection; Medical research; Medicine, Experimental; Mice, Inbred BALB C; Models, Biological; Molybdenum alloys; Organometallic Compounds - adverse effects; Organometallic Compounds - pharmacology; Phthalocyanins; Prevention; Sulfates; Sulfates - adverse effects; Sulfates - pharmacology; Treatment Outcome
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-015-0358-5

Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally.
CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90.
CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 μg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 μg/mL.
These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.