This technology includes the identification and use of niclosamide analogs and prodrugs for the treatment of SARS-CoV-2 infection. In-vitro studies have found niclosamide, an old anthelminthic drug, to be potent and effective against Covid-19. But the broad antiviral effect of niclosamide is offset by the low solubility of the drug, leading to poor oral absorption. The niclosamide analogs and prodrugs included in this technology have better in vitro physicochemical properties. Also, these analogs were comparable to niclosamide in the in-vitro 3D models of SARS-CoV-2 infection.

This technology includes the identification and use of a combination therapy consisting of human recombinant N-acetylgalactosamine-6-sulfate sulfatase (hrGALNS) and the pharmacological chaperone compounds Ezetimibe and Pranlukast for the treatment of Mucopolysaccharidosis Type IVA (MPS IVA). MPS IVA is a rare disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Currently, hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are available for patients with MPS IVA.

The current invention provides nucleic acid sequences comprising the genomes of infectious hepatitis C viruses (HCV) of genotype 1a and 1b. It covers the use of these sequences, and polypeptides encoded by all or part of the sequences, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.

Local inflammation processes are crucially important in the host defense against pathogens and for successful immunization because proinflammatory cytokines are necessary for initiation and propagation of an immune response. However, normal inflammatory responses are eventually terminated by physiological termination mechanisms, thereby limiting the strength and duration of immune responses, especially to weak antigens. The inventors have shown that adenosine A2a and A3a receptors play a critical role in down-regulation of inflammation in vivo.

Homocystinuria (HCU), a group of inherited disorders, causes symptoms ranging from failure to thrive and developmental delays in infants or young children to abnormal blood clots with onset in adults.1 Approximately 1 in 200,000 to 335,000 people have HCU globally.2

ADP-ribosylation of arginine residues in proteins may be involved in cell adhesion and is crucial for the action of cholera toxin and E. coli heat-labile enterotoxin, agents involved in the pathogenesis of cholera and traveller's diarrhoea, respectively. ADP-ribosylation is reversed by ADP-ribosylarginine hydrolases, which cleave the ADP-ribose-arginine bond. ADP-ribosylarginine hydrolases from a variety of mammalian species and tissues were isolated, and the coding regions for the hydrolases were cloned and expressed.

Filamentous phage-based display systems have found widespread use in molecular biology, including many immunologic applications such as antigen presentation and the immuno-isolation of desired recombinants by "biopanning".

Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. The present invention is directed toward vector stage replication-defective flaviviruses that are replication-defective in mosquito vectors that transmit them to humans. The replication-defective flaviviruses of the present invention demonstrate a limited ability to replicate in the vector organisms that transmit flaviviruses from one host to another.

The current invention provides a nucleic acid sequence comprising the genome of infectious hepatitis C viruses (HCV) of genotype 2a. The encoded polyprotein differs from those of the infectious clones of genotypes 1a and 1b (U.S. Patent 6,153,421) by approximately thirty (30) percent. It covers the use of this sequence and polypeptides encoded by all or part of the sequence, in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV. Additional information can be found in Yanagi et al.

The current invention provides nucleic acid sequences comprising chimeric viral genome of hepatitis C Virus (HCV) and bovine viral diarrhea viruses (BVDV). The chimeric viruses are produced by replacing the structural region or a structural gene of an infectious BVDV clone with the corresponding region or gene of an infectious HCV. It covers the use of these sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and the development of screening assays for the identification of antiviral agents for HCV.