Human immunodeficiency virus type 1 nucleocapsid inhibitors impede trans infection in cellular and explant models and protect nonhuman primates from infection.
Here, we report that the S-acyl-2-mercaptobenzamide thioester (SAMT) class of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NCp7) inhibitors was able to prevent transmission of HIV-1 from infected cells, including primary cells. Furthermore, when SAMTs were introduced during an HIV-1 challenge of cervical explant tissue, inhibition of dissemination of infectious virus by cells emigrating from the tissue explants was observed. Preliminary studies using a rhesus macaque vaginal challenge model with mixed R5 and X4 simian-human immunodeficiency virus infection found that five of six monkeys were completely protected, with the remaining animal being partially protected, infected only by the R5 virus. These data suggest that SAMTs may be promising new drug candidates for further development in anti-HIV-1 topical microbicide applications.
Wallace
Gregory S
GS
St George's University of London, United Kingdom.
Cheng-Mayer
Cecilia
C
Schito
Marco L
ML
Fletcher
Patricia
P
Miller Jenkins
Lisa M
LM
Hayashi
Ryo
R
Neurath
A Robert
AR
Appella
Ettore
E
Shattock
Robin J
RJ
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D008253:Macaca mulatta; D019251:Nucleocapsid / Q000187:drug effects; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors*
D019380:Anti-HIV Agents; C071884:NCP7 protein, Human immunodeficiency virus 1; D054301:gag Gene Products, Human Immunodeficiency Virus