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Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120.

Neurath AR, Strick N, Li YY, Debnath AK - BMC Infect. Dis. (2001)

Bottom Line: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses.CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus.These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biochemical Virology Laboratory, The Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA. arneurath@worldnet.att.net

ABSTRACT

Background: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus.

Methods: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope.

Results: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus.

Conclusions: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection.

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Binding of CAP treated and untreated HIV-1 IIIB to wells coated with antibodies to peptides from gp120/gp41 [reference 16]. Experimental conditions were similar to those described in the legend for Fig. 3. The absorbance corresponding to untreated HIV-1 captured onto the wells was in the range of 0.09 to 0.37. The absorbance corresponding to controls (virus captured onto wells coated with Protein A followed by normal rabbit serum) was 0.014. Numbering of gp160 amino acid residues was the same as in reference 16. Decreases of CAP treated virus binding, as compared with binding of control virus, were plotted.
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Figure 4: Binding of CAP treated and untreated HIV-1 IIIB to wells coated with antibodies to peptides from gp120/gp41 [reference 16]. Experimental conditions were similar to those described in the legend for Fig. 3. The absorbance corresponding to untreated HIV-1 captured onto the wells was in the range of 0.09 to 0.37. The absorbance corresponding to controls (virus captured onto wells coated with Protein A followed by normal rabbit serum) was 0.014. Numbering of gp160 amino acid residues was the same as in reference 16. Decreases of CAP treated virus binding, as compared with binding of control virus, were plotted.

Mentions: The binding of control and CAP-treated HIV-1 IIIB to antibodies against peptides derived from gp120/gp41 [16] was also determined. In agreement with the results obtained using mAbs, CAP treatment resulted in most pronounced decreases of virus binding to antibodies against peptide 303–338 (= V3 loop) and the adjacent peptide 280–306 (Fig. 4).


Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120.

Neurath AR, Strick N, Li YY, Debnath AK - BMC Infect. Dis. (2001)

Binding of CAP treated and untreated HIV-1 IIIB to wells coated with antibodies to peptides from gp120/gp41 [reference 16]. Experimental conditions were similar to those described in the legend for Fig. 3. The absorbance corresponding to untreated HIV-1 captured onto the wells was in the range of 0.09 to 0.37. The absorbance corresponding to controls (virus captured onto wells coated with Protein A followed by normal rabbit serum) was 0.014. Numbering of gp160 amino acid residues was the same as in reference 16. Decreases of CAP treated virus binding, as compared with binding of control virus, were plotted.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC57811&req=5

Figure 4: Binding of CAP treated and untreated HIV-1 IIIB to wells coated with antibodies to peptides from gp120/gp41 [reference 16]. Experimental conditions were similar to those described in the legend for Fig. 3. The absorbance corresponding to untreated HIV-1 captured onto the wells was in the range of 0.09 to 0.37. The absorbance corresponding to controls (virus captured onto wells coated with Protein A followed by normal rabbit serum) was 0.014. Numbering of gp160 amino acid residues was the same as in reference 16. Decreases of CAP treated virus binding, as compared with binding of control virus, were plotted.
Mentions: The binding of control and CAP-treated HIV-1 IIIB to antibodies against peptides derived from gp120/gp41 [16] was also determined. In agreement with the results obtained using mAbs, CAP treatment resulted in most pronounced decreases of virus binding to antibodies against peptide 303–338 (= V3 loop) and the adjacent peptide 280–306 (Fig. 4).

Bottom Line: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses.CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus.These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biochemical Virology Laboratory, The Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA. arneurath@worldnet.att.net

ABSTRACT

Background: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus.

Methods: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope.

Results: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus.

Conclusions: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection.

Show MeSH
Related in: MedlinePlus