In The present invention relates in a first aspect to the use of influenza virus defective interfering particles in the prophylactic or therapeutic treatment of coronaviridae infection. In particular, it has been recognized that defective interfering particles of influenza A have beneficial effects in the treatment of SARS coronavirus infection, in particular, SARS-CoV-2 infection. Further, the present invention relates to a pharmaceutical composition for use in treating coronaviridae infection, in particular SARS-CoV-2. In a further aspect, methods for the prophylactic or therapeutic treatments of coronaviridae based on the administration of DIFs are disclosed.

The disclosure provides for methods for making and using modified influenza gene products, alone or in combination, e.g., to inhibit wild-type influenza virus replication, to serve as an immunostimulatory agent, and/or as attenuated vaccine backbones. In one embodiment, the genomes of the DIPs provide for inhibitory activity, producing a dual effect in which both the RNA itself and the encoded protein coordinate to interfere with replication. Thus, the ability of DIPs to block replication of WT virus provides for a treatment for infection, use as an immunostimulatory agent, and as attenuated viruses for vaccination.

The present invention provides a recombinant influenza virus vector comprising an NS gene encoding a truncated NS1 protein of at least 73 and up to 122 amino acids of the N-terminus of the respective wild type NS1 protein, wherein the vector replicates in IFN-sensitive tumor cells and does not replicate in normal, non-tumor cells, and expresses a heterologous immunostimulatory polypetide. The invention further provides a pharmaceutical composition containing the influenza virus vector, its use for the treatment of cancer patients and methods for producing the influenza virus vaccine.

The present invention provides a recombinant influenza virus vector comprising an NS gene encoding a truncated NS1 protein of at least 73 and up to 122 amino acids of the N-terminus of the respective wild type NS 1 protein, wherein said vector replicates in IFN-sensitive tumor cells and does not replicate in normal, non-tumor cells, and expresses a heterologous immunostimulatory polypetide. The invention further provides a pharmaceutical composition containing said influenza virus vector, its use for the treatment of cancer patients and methods for producing said influenza virus vaccine.

The present invention is the use of designed recombinant viruses for the treatment of various forms of malignant tumors. The recombinant viruses of the invention are those in which one or more regions of the wild type virus was exchanged with a synthetic recoded sequence that reduces the codon pair score relative to human codon pair bias, or that increase the number for CpG di-nucleotides, or that increases the number of UpA di-nucleotides. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, skin, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, as well as for the treatment of breast cancer and melanoma as well.

The present invention provides a modified influenza A virus (IAV) comprising, consisting of, or consisting essentially of at least one artificial gene segment comprising a duplicated packaging signal, the result of which is a modified IAV that is replication competent and avirulent, and when co-infected with a wild type virus leads to segment exchange and compromises the spread of both viruses as well as methods of making and using same and methods of using the IAVs in the treatment and prevention of influenza-related diseases.