CRISPR RNA-guided nucleases are routinely used for sequence-specific manipulation of DNA. While CRISPR-based DNA editing has become routine, analogous methods for editing RNA have yet to be established. Here we repurpose the type III-A CRISPR RNA-guided nuclease for sequence-specific cleavage of the SARS-CoV-2 genome. The type III cleavage reaction is performed in vitro using purified viral RNA, resulting in sequence-specific excision of 6, 12, 18 or 24 nucleotides. Ligation of the cleavage products is facilitated by a DNA splint that bridges the excision and RNA ligase is used to link the RNA products before transfection into mammalian cells. The SARS-CoV-2 RNA is infectious and standard plaque assays are used to recover viral clones. Collectively, this work demonstrates how type III CRISPR systems can be repurposed for sequence-specific editing of RNA viruses including SARS-CoV-2 and more generally for gene therapy.

The present invention relates to a Corona antigen comprising a Corona nucleocapsid specific amino acid sequence, compositions, and reagent kits comprising the same and methods of producing it. Also encompassed are methods of detecting anti-Corona antibodies in samples using said Corona antigen, and methods of differential diagnosis of an immune response in a patient due to natural Corona infection or due to vaccination against Corona.

The present invention provides myxoma viral vectors that encode severe acute respiratory syndrome coronavirus 2 antigens and that can facilitate expression and secretion of virus-like particles (VLPs). Also provided are methods of making said VLPs in mammalian cells and using said VLPs and myxoma viral vectors to induce an immune response in a subject.

RNA replicon derived from a coronavirus with complete or partial deletion of: the gene encoding the E protein and at least 4 genes encoding genus accessory proteins selected from: 3, 4a, 4b and 5, in the case of MERS-CoV. Method of preparation thereof, and their use in vaccine compositions.

The present disclosure relates to a system for and a method of incorporating SARS-CoV-2 genes and proteins into T4 phages. The present disclosure also relates to vaccine against SARS-CoV-2 containing recombinant T4 phages created using the method provided in the present disclosure.

Provided herein are vaccines against coronavirus that utilize adeno-associated virus (AAV) for delivery.

The present description relates to a Corona antigen having a Corona nucleocapsid specific amino acid sequence, compositions, and reagent kits having the same and methods of producing it. Also encompassed are methods of detecting anti-Corona antibodies in samples using the Corona antigen, and methods of differential diagnosis of an immune response in a patient due to natural Corona infection or due to vaccination against Corona.

Provided are a bovine rotavirus fusion protein and calf diarrhea multivalent vaccine. The bovine rotavirus fusion protein contains a VP6 fragment, wherein the VP6 fragment contains an amino acid sequence as represented by SEQ ID NO. 4, and at least one loop region of the following (a)˜(c) is substituted with an antigenic epitope derived from bovine coronavirus and/or an antigenic epitope derived from E. coli: (a) amino acid residues of sites 168-177, with an amino acid sequence as represented by SEQ ID NO. 1; (b) amino acid residues of sites 194-205, with an amino acid sequence as represented by SEQ ID NO. 2; and (a) amino acid residues of sites 296-316, with an amino acid sequence as represented by SEQ ID NO. 3, The bovine rotavirus fusion protein contains a plurality of antigenic epitopes, and can enable a host to generate a plurality of antibodies after immunizing the host.

The present application relates to SARS-CoV-2 virus-like particles (VLP) and related plasmids, compositions, and methods. The VLP can comprise a modified spike glycoprotein, a matrix protein, a nucleoprotein N and an envelope protein of SARS-CoV-2, where the modified spike glycoprotein comprises an S1 domain and an S2 domain, and includes one or more modifications. These modifications can include: linking the S1 and S2 domains via generation of disulfides bonds between the S1 and S2 domains; linking intra-polypeptide and inter-polypeptide S2 helices of the S2 domain; and substitution of one or more non-cysteine residues with a cysteine residue to generate one or more disulfide bonds. The modifications can stabilize a prefusion conformation of the spike glycoprotein and prohibit a transition to a post-fusion structure.

The present invention addresses the problem of providing a more convenient method for in vitro proliferating a virus belonging to the family Coronaviridae at high proliferation accuracy. This problem is solved by an in vitro virus proliferation method, said method comprising a step for culturing kidney-derived cells, which have been contacted with the virus belonging to the family Coronaviridae, with a use of a cell culture medium to which a protease having an optimum pH of from 7 to 9 is added.