New York Blood Center, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

National Institutes of Health

Asim Kumar Debnath

Francesca Curreli

Shibo Jiang

Peter D Kwong

Young Do Kwon

Alexander Robert Neurath

Hongtao Zhang

Nathan Strick

Gordon Jay Dow

Qian Zhao

Yun-Yao Li

Substituted phenylpyrrolecarboxamide compounds such as those represented by Formula A can be used in the treatment of HIV infection and related conditions.

Substituted phenylpyrrolecarboxamides with therapeutic activity in HIV

Chemical compounds that inhibit retroviruses are presented herein. More particularly, this disclosure provides small molecule compounds that inhibit infection with, or treat infection caused by, human immunodeficiency viruses.

HIV inhibitors

Provided are constrained peptides that inhibit HIV assembly. Pharmaceutical compositions comprising the above peptides are also provided. Additionally provided are methods of inhibiting replication of a capsid-containing virus in a cell. Also provided are methods of treating a mammal infected with a capsid-containing virus. Further provided are methods of treating a mammal at risk for infection with a capsid-containing virus. Methods of making the above peptides are additionally provided, as are uses of the above peptides and pharmaceutical compositions.

Stabilized therapeutic small helical antiviral peptides

Provided are constrained peptides that inhibit HIV assembly. Pharmaceutical compositions comprising the above peptides are also provided. Additionally provided are methods of inhibiting replication of a capsid-containing virus.

Disclosed herein are cell penetrating peptides useful as treatment for Human Immunodeficiency Virus.

Antiviral cell-penetrating peptides

Chemical compounds that disrupt retroviral assembly and maturation are presented herein. More particularly, this disclosure provides small molecule compounds that disrupt the formation and maturation of virus particles and methods of using such small molecules to treat HIV-1 infection.

Small molecule inhibitors of retroviral assembly and maturation

A group of compounds that inhibit HIV replication by blocking HIV entry was identified. Two representative compounds, designated NB-2 and NB-64, inhibited HIV replication (p24 production) with ICvalues &#x3c;0.5 &#x3bc;g/ml. It was proved that NB-2 and NB-64 are HIV entry inhibitors by targeting the HIV gp41 since: 1) they inhibited HIV-mediated cell fusion; 2) they inhibited HIV replication only when they were added to the cells less than one hour after virus addition; 3) they did not block the gp120-CD4 binding; 4) they did not interact with the coreceptor CXCR4 since they failed to block anti-CXCR4 antibody binding to CXCR4-expressing cells; 5) they blocked the formation of the gp41 core that is detected by sandwich enzyme linked immunosorbent assay (ELISA) using a conformation-specific MAb NC-1; 6) they inhibited the formation of the gp41 six-helix bundle revealed by fluorescence native-polyacrylamide gel electrophoresis (FN-PAGE); and 7) they blocked binding of D-peptide to the hydrophobic cavity within gp41 coiled coil domain, modeled by peptide IQN17. These results suggested that NB-2 and NB-64 may interact with the hydrophobic cavity and block the formation of the fusion-active gp41 coiled coil domain, resulting in inhibition of HIV-1 mediated membrane fusion and virus entry.

Compounds for inhibition of HIV infection by blocking HIV entry

A method of preventing HIV-1 or HIV-2 infection by administering to a human a pharmaceutically effective anti-HIV-1 or anti-HIV-2 amount of a tin or silicon protoporphyrin IX or tin or silicon mesoporphyrin IX, or a pharmaceutically acceptable salt thereof.

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Fort Lee, NJ, United States of America

Asim Kumar Debnath