Abstract: Provided herein are methods, pharmaceutical compositions, and kits for treating and/or preventing a viral infection resulting from a coronaviridae family virus in a subject in need thereof, comprising administering to the subject a compound of Formula (I), or a pharmaceutical composition comprising a compound of Formula (I). Further provided herein are methods for inhibiting the viral entry into a cell of a coronaviridae family virus (e.g., alpha-coronavirus (e.g., HCoV-NL63, HCoV-229E), betacoronavirus (e.g., SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-HKU1)) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I) as described herein.

Abstract: Antibodies (e.g., sdAbs) binding to PCSK9 are described. Nucleic acids encoding such Abs, host cells expressing such Abs and pharmaceutical composition comprising same are described. The use of these PCSK9-binding Abs for lowering low-density lipoprotein-cholesterol (LDL-C) levels and for the treatment of cardiovascular disorders, is also described.

Abstract: A compound of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, or racemic mixture or stereoisomer thereof, and methods for preventing or treating an LDL-cholesterol-related disease or disorder using such compound(s), and kits and compositions comprising such compound(s).

Abstract: Antibodies (e.g., sdAbs) binding to PCSK9 are described. Nucleic acids encoding such Abs, host cells expressing such Abs and pharmaceutical composition comprising same are described. The use of these PCSK9-binding Abs for lowering low-density lipoprotein-cholesterol (LDL-C) levels and for the treatment of cardiovascular disorders, is also described.

Abstract: A method for identifying a compound for preventing or treating a LDLR-associated disease, a VLDLR-associated disease or an ApoER2-associated disease, said method comprising determining whether: a) a level of expression of Annexin A2 nucleic acid or encoded polypeptide; b) a level of Annexin A2 activity; or c) a combination of a) and b), is increased in the presence of a test compound relative to in the absence of said test compound, wherein said increase is indicative that said test compound can be used for preventing or treating a LDLR-associated disease, a VLDLR-associated disease, an ApoER2-associated disease.

Abstract: A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

Abstract: A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

Abstract: A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

Abstract: A method for treating and/or preventing a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9)-susceptible viral infection comprising increasing a PCSK9 activity and/or expression in a biological system infected by the virus, whereby the increased PCSK9 activity and/or expression treats and/or prevents the viral infection in the biological system. Methods of classifying subjects, methods of screening and kits therefore.

Abstract: A method for identifying a compound for preventing or treating a LDLR-associated disease, a VLDLR-associated disease or an ApoER2-associated disease, said method comprising determining whether: a) a level of expression of Annexin A2 nucleic acid or encoded polypeptide; b) a level of Annexin A2 activity; or c) a combination of a) and b), is increased in the presence of a test compound relative to in the absence of said test compound, wherein said increase is indicative that said test compound can be used for preventing or treating a LDLR-associated disease, a VLDLR-associated disease, an ApoER2-associated disease.

Abstract: A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

Abstract: A method for treating and/or preventing a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9)-susceptible viral infection comprising increasing a PCSK9 activity and/or expression in a biological system infected by the virus, whereby the increased PCSK9 activity and/or expression treats and/or prevents the viral infection in the biological system. Methods of classifying subjects, methods of screening and kits therefore.

Abstract: The present invention discloses the identification of a human hypercholesterolemia causal gene, which can be used for the diagnosis, prevention and treatment of hypercholesterolemia, more particularly familial hypercholesterolemia, as well as for the screening of therapeutically active drugs. The invention more specifically disclosed that mutations in the PCSK9 gene encoding NARC-1 causes autosomal dominant hypercholesterolemia and represent novel targets for therapeutic intervention. The invention can be used in the diagnosis of predisposition to, detection, prevention and/or treatment of coronary heart disease and, cholesterol, lipid and lipoprotein metabolism disorders, including familial hypercholesterolemia, atherogenic dyslipidemia, atherosclerosis, cardiovascular diseases.

Abstract: Using RT-PCR and degenerate oligonucleotides derived from the active site residues of subtilisin-kexin-like serine proteinases, we have identified a highly conserved and phylogenetically ancestral human, rat and mouse type-I membrane-bound proteinase called subtilisin-kexin-isozyme-1 (SKI-1). Computer data bank searches reveals that human SKI-1 was previously cloned but with no identified function. A SKI-1 processed fragment is secreted in culture media in a soluble form. In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of proBDNF. Peptides mimicking SKI-1 cleavages sites are also disclosed. SKI-1 prosegment has an ex vivo inhibitory effect on SKI-1 activity. The prosegment is also processed and secreted in culture media. One of its fragments is found tightly associated with the SKI-1 soluble form. Therapeutic applications for SKI-1 inhibitors are disclosed.

Abstract: The present invention discloses the identification of a human hypercholesterolemia causal gene, which can be used for the diagnosis, prevention and treatment of hypercholesterolemia, more particularly familial hypercholesterolemia, as well as for the screening of therapeutically active drugs. The invention more specifically disclosed that mutations in the PCSK9 gene encoding NARC-1 causes autosomal dominant hypercholesterolemia and represent novel targets for therapeutic intervention. The invention can be used in the diagnosis of predisposition to, detection, prevention and/or treatment of coronary heart disease and, cholesterol, lipid and lipoprotein metabolism disorders, including familial hypercholesterolemia, atherogenic dyslipidemia, atherosclerosis, cardiovascular diseases.

Abstract: A novel Asp-ase activity, referred to as BACE secretase/sheddase, has been found to cleave the ectoddomain of BACE after Asp379 (SQDD↓) and Asp407 (VVFD↓), and likely after Asp451 (PQTD↓). The cleavage of BACE by BACE secretase/sheddase renders BACE soluble which in turns appears to enhance the generation of the amyloidogenic peptide A&bgr;, which has been implicated as a major factor in the etiology of Alzheimer's Disease. The current invention concerns the modulation of this novel BACE secretase/sheddase activity for such applications as the prevention or treatment of a neurodegenerative disorder that is characterized by the generation of A&bgr; protein, including Alzheimer's Disease.

Abstract: The present invention relates to the cloning of human pro-protein converting enzyme 5 (PC5) CDNA isolated from human adrenal gland messenger RNA. Additionally, this invention relates to a method for reducing restenosis occurring at an injured vascular site comprising delivering to the injured site an antisense nucleic acid to suppress the expression of human PC5.

Abstract: This invention relates to a novel and seventh member of the subtilisin-kexin family isolated from rat, which has been named rPC7. The rat spleen cDNA has been totally sequenced. A shorter DNA sequence has been obtained for human, which corresponds to a portion of the catalytic region of a human pro-hormone convertase corresponding to the rat pro-hormone convertase. PC7 clearly distinguishes from the other mammalian members of the subtilisin-kexin family. Its tissue distribution is ubiquitous, but its presence is particularly remarkable in lymphoid tissues. It is present in LoVo cells that are able to cleave the HIV gp160 protein into active gp120/gp41 proteins and that are deficient in other effective pro-hormone convertases known up to date. Therefore, it is proposed that PC7 is a good candidate as a maturation enzyme responsible for the conversion of HIV gp160 protein in target CD.sup.+4 cells.

Abstract: The present invention relates to pro-hormone convertases and polypeptidic fragments thereof, nucleic acids encoding them, recombinant viruses expressing these convertases, polyclonal antibodies directed against the convertases, diagnostic kits for the detection and measurement of the convertase content in cell or tissue lysates, culture media or biological fluids by RIA. Diagnostic kits were also developped for detection or measurement of nucleic acids, preferably mRNAs, in cell or tissue lysates by hybridization. The invention also concerns oligonucleotides useful as probes or as primers for DNA synthesis. These oligonucleotides were included in the diagnostic kits as well as used for the obtention of specific fragments of the convertases which have served, together with native convertases, as antigens for the obtention of antibodies. The convertases were produced by mammalian cell lines transfected with the recombinant viruses and purified on affinity columns which are also an object of the invention.

Abstract: There are disclosed the N-terminal fragment of human pro-opiomelanocortin, a glycopeptide composed of 76 amino acid residues, and a process for preparing same from human pituitary glands. The glycopeptide is useful in potentiating the effects of ACTH on steroidogenesis, in stimulating the production of aldosterone, as a diagnostic tool, as well as a reagent for determining its presence in biological fluids and tissues by immunochemical means.