Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120.
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.
Neurath
A R
AR
Biochemical Virology Laboratory, The Lindsley F Kimball Research Institute of the New York Blood Center, New York, NY 10021, USA. arneurath@worldnet.att.net
Strick
N
N
Li
Y Y
YY
Debnath
A K
AK
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000494:pharmacology; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011991:Receptors, Virus / Q000037:antagonists & inhibitors*
D019380:Anti-HIV Agents; D005079:Excipients; D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus; D002482:Cellulose; C011708:cellulose acetate phthalate