The Picower Institute for Medical Research

Washington University

Cytokine Pharmasciences, Inc.

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

University of California

Lead Discovery Center Gmbh

Baker Heart and Diabetes Research Institute.

Michael I Bukrinsky

Anthony Cerami

Peter C Ulrich

Kevin J Tracey

Pamela Cohen

Helena Schmidtmayerova

Ruth Hunegnaw

Alexei Adzhubei

Gunter Fischer

Omar K Haffar

Dmitri Sviridov

Senliang Pan

Bradley Berger

Stephanie Constant

Frank Erdmann

Miroslav Malesevic

Gerd Ruhter

Peter Nussbaumer

Barbara A Sherry

Gerd Rühter

Jan Kühling

Yury Miller

Massimo Alfano

Klaus Dinkel

Bradley J Berger

In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for preventing or slowing the spread of a viral infection, wherein optionally the viral infection is a coronavirus infection, optionally a COVID-19 infection or variant thereof, or a human immunodeficiency virus (HIV) infection, preventing or decreasing coronavirus or HIV-co-morbidities in an individual, or inhibiting, or slowing the rate of, coronavirus (optionally COVID-19) or HIV replication in vitro and in vivo.

Compositions and methods to treat viral infection and co-morbidities

The invention relates to compounds and methods for restoring or preserving cholesterol efflux in a cell infected with Human Immunodeficiency Virus (HIV) by preventing or decreasing an interaction between Negative Regulatory Factor (Nef) protein and Calnexin protein, and methods for screening for such compounds.

Compounds inhibiting Nef-calnexin interaction

The present invention relates to novel cyclosporin derivatives that do not cross the cellular membrane. The compounds according to the invention are used in medicine, more particularly in the treatment/diagnosis of acute and chronic inflammatory diseases, viral infections, cancer, degenerative muscle diseases, neurodegenerative diseases and damage that is associated with calcium homeostasis impairment. The novel cyclosporin derivatives additionally have no immunosuppressive effect.

Cyclosporin derivatives

A cyclosporin derivative of general Formula (I) or a pharmaceutically compatible salt thereof, which have a pharmaceutical effectiveness, for example in the case of chronic inflammatory diseases. The cyclosporin derivatives are preferably free from a peptide section capable of passing through the membrane of a biological cell.

The present invention provides novel methods for treating and preventing coronary artery disease in HIV-1-infected individuals by interfering with Nef-mediated effect on ABCA1. The invention further provides novel methods for suppressing HIV infection by stimulating cholesterol efflux from cells by stimulating expression of ABCA1 in HIV-1-infected individuals. These methods take advantage of the finding that Nef, a regulatory protein of HIV-1, (1) diminishes expression of ATP-binding cassette transporter A1 (ABCA1), the main transporter of cholesterol from cells to extracellular acceptors; and (2) impairs cholesterol efflux from HIV-1-infected macrophages leading to cholesterol accumulation and formation of foam cells, which is a characteristic feature of atherosclerosis.

Method of suppressing human immunodeficiency virus (HIV) replication in a subject by administering a liver X receptor (LXR) agonist

There is disclosed a method for treating diseases and disorders involving T cell activation and HIV-infection using the p38 mitogen activated protein kinase (MAPK) signaling pathway as a target for intervention. There is further disclosed a use for guanylhydrazone-substituted compounds to treat diseases and disorders related to T cell activation and HIV-infection.

Guanylhydrazones useful for treating diseases associated with T cell activation

The present invention concerns alkyl aryl carbonyl compounds that possess anti-infective activity. The compounds of the invention can be used to target specific nuclear localization signal, thereby blocking importation of specific proteins or molecular complex into the nucleus of a cell. The invention encompasses methods of use of such compounds for treatment or prevention of infectious diseases, such as parasitic and viral diseases, including, for example, malaria and acquired immunodeficiency syndrome. The use of the compounds to detect certain specific protein structures which are present in nuclear localization sequences is also taught.

Compounds and methods of use to treat infectious diseases

There is disclosed a method for treating diseases and disorders involving T cell activation and HIV-infection, using the p38 mitogen activated protein kinase (MAPK) signaling pathway as a target for intervention. There is further disclosed a use for guanylhydrazone-substituted compounds to treat diseases and disorders related to T cell activation and HIV-infection.

Guanylhydrazones useful for treating diseases associated with T cell

There is disclosed a method for anti-viral therapy treatment with the Pertussis toxin beta subunit oligomer, wherein the oligomer is composed of from two to ten subunits of PTX selected from the group consisting of S2, S3, S4, S5, and combinations thereof.

Anti-viral treatment with pertussis toxin B oligomer

There is disclosed a structural genus of compounds, defined according to coordinates in three-dimensional space, that binds amino moieties on neighboring lysine residues in a tyrosine residue 29 pocket of the matrix protein component of the HIV preintegration complex (PIC), thereby preventing the PIC from binding to karyopherin .alpha. and preventing nuclear importation and integration of the HIV viral genome into the host cell DNA, thereby preventing viral infection.

HIV matrix protein tyrosine position 29 pocket binders

There is disclosed compound according to the formula: ##STR1## wherein A, independently,=CH.sub.3 or CH.sub.2 CH.sub.3, P=1 or 2; and ##STR2## wherein X=NH.sub.2, CH.sub.3 or CH.sub.2 CH.sub.3 ; X'=CH.sub.3 or CH.sub.2 CH.sub.3 ; Y=NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 ; and Z=H, CH.sub.3 or CH.sub.2 CH.sub.3 ; or ##STR3## wherein Y' and Z', independently,=H, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2 or N.sup.+ (CH.sub.3).sub.3 ; Q is N or CH; and salts thereof.

Growing community of inventors

Glenwood Landing, NY, United States of America

Michael I Bukrinsky