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

Other

The United States of America As Represented by the Department of Health

William G Rice

James A Turpin

Louis E Henderson

Larry K Keefer

Christopher J Michejda

Ettore Appella

Joseph E Saavedra

John K Inman

Xinhua Ji

Mingjun Huang

Larry O Arthur

David Covell

Marek W Cholody

Yongsheng Song

Aloka Srinivasan

Anders Wallqvist

Christian Bogdan

Andrew Maynard

Mark Stanley Cushman

Agustin Casimiro-Garcia

David C Baker

Douglas D Buechter

Christopher W Marlor

Xiaohong Hou

Wengang Yang

Robert R Schultz

Alan R Rein

This invention pertains to the discovery of a novel family of thiolesters and uses thereof. Also provided for are viricidal compounds and pharmaceutical formulations comprising these novel thiolesters. The invention also provides thiolester-inactivated viruses and thiolester-complexed viral proteins.

Thiolesters and uses thereof

The present invention relates to methods of identifying a molecule from a library of molecules that inhibits binding of human immunodeficiency virus nucleocapsid 7 polypeptide (NCp7) to an oligonucleotide which comprises admixing an NCp7 polypeptide with at one labeled HIV-1 psi-site oligonucleotide and an amount of the molecule to be tested under binding conditions; and determining the amount of oligonucleotide bound to the NCp7 polypeptide, wherein a decrease in the amount of oligonucleotide bound in the presence of the molecule compared with the amount of oligonucleotide bound in the absence of the molecule indicates that the molecule inhibits binding of NCp7 polypeptide to the oligonucleotide.

Methods for identifying compounds which inhibit binding of nucleocapsid 7 protein to HIV-1 RNA

The present invention provides several classes of compounds which can be used to inactivate retroviruses, such as HIV-1, by attacking the CCHC zinc fingers of the viral nucleocapsid protein and ejecting the zinc therefrom. In addition, kits for identifying compounds that can react with CCHC zinc fingers of the nucleocapsid proteins of a large number of different retroviruses have also been developed. The kits of the present invention describe a set of specific tests and reagents that can be used to screen and identify compounds based on their ability to react with and disrupt retroviral zinc fingers in the viral NC proteins and, in turn, inactivate the retrovirus of interest.

Method for identifying and using compounds that inactivate HIV-1 and other retroviruses by attacking highly conserved zinc fingers in the viral nucleocapsid protein

Provided are O-glycosylated 1-substituted diazen-1-ium-1,2-diolates (O-glycosylated diazeniumdiolates) having the formula:in which R is a saccharide, which is attached to the Oof the compound by the anomeric carbon of a pyranose ring or a furanose ring.

O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates

Diazeniumdiolates, wherein the N position is substituted by an inorganic or organic moiety and the O -oxygen is bound to a substituted or unsubstituted aromatic group, are provided. Also provided are O -glycosylated 1-substituted diazen-1-ium-1,2-diolates (O -glycosylated diazeniumdiolates) and O -substituted 1-&lsqb;(2-carboxylato)pyrrolidin-1-yl&rsqb;diazen-1-ium-1,2-diolates (1-&lsqb;(2-carboxylato)pyrrolidin-1-yl&rsqb;diazeniumdiolates). The O -aryl diazeniumdiolates are stable with respect to the hydrolytic generation of nitric oxide in neutral to acidic solutions and generate nitric oxide in basic or nucleophilic environments or microenvironments. Also provided are compositions, including pharmaceutical compositions, comprising such compounds and methods of using such compounds.

O2-arylated or O2-glycosylated 1-substituted diazen-1-ium-1,2-diolates and O2-substituted 1-&lsqb;(2-carboxylato) pyrrolidin-1-yl&rsqb; diazen-1-ium-1,2-diolates

Alkenyldiarylmethane (ADAM) compounds have been found effective as anti-HIV agents. Novel ADAM compounds, their pharmaceutical formulations and a method of using same to treat viral infections are described.

Alkenyldiarylmethane non-nucleoside HIV-1 reverse transcriptase inhibitors

Acridone-derived compounds useful as antineoplastic and antiretroviral agents

The present invention relates to several novel acridone-derived compounds of of formula (I) or (II). These compounds are potent anti-viral agents, useful in the treatment of viral diseases, such as Human Immunodeficiency Virus. In addition, these compounds are anti-neoplastic agents useful in the treatment of various forms of cancer.

Anti-viral pharmaceutical compositions containing saturated

Method for identifying and using compounds that inactivate HIV-1 and

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Frederick, MD, United States of America

William G Rice