Disclosed are novel targets for coronavirus therapies and methods of their use in screens for novel inhibitors of coronaviral infections. Also disclosed are novel coronavirus inhibitors that interact with said targets.

Timely development of vaccines and antiviral drugs is critical to control the COVID-19 pandemic. Current methods for quantifying vaccine-induced neutralizing antibodies involve the use of pseudoviruses, such as the SARS-CoV-2 spike protein (S) pseudotyped lentivirus. However, these pseudoviruses contain structural proteins foreign to SARS-CoV-2, and require days to infect and express reporter genes. Here, the present application discloses composition and methodology for making and using a new hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) particle for rapid and accurate quantification of neutralization antibodies and viral variants.

This invention relates to SARS-CoV-2 viruses adapted with nanoluciferase reporter molecules and mouse-adapted SARS-CoV-2 viruses, compositions including the same and methods of use thereof.

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 disclosure provides virus like nanoparticles (VLPs), which are capable of displaying multiple copies of a SARS-CoV-2 antigen, for eliciting protective immunity against a SARS-CoV-2 infection, as well as polypeptides, compositions and methods thereof.

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 disclosure provides Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) vaccines, recombinant vesicular stomatitis virus (VSV) vectors encoding the SARS-CoV-2 spike (S) protein or an immunogenic variant thereof, recombinant replicable VSV particles having a SARS-CoV-2 S protein or an immunogenic variant thereof on the surface of the particles, and immunogenic recombinant proteins comprising a SARS-CoV-2 S protein or a variant thereof. Immunogenic compositions comprising the SARS-CoV-2 vaccines, the recombinant VSV vectors, the recombinant replicable VSV particles and/or the immunogenic recombinant proteins may be used for inducing an immune response to the SARS-CoV-2, preventing infection by the SARS-CoV-2, vaccinating against the SARS-CoV-2 and/or producing adaptive mutants of the recombinant replicable VSV particles.

The present disclosure is directed to a recombinant nucleic acid construct encoding a defective interfering coronaviridae virus particle. The recombinant construct comprises: a nucleotide sequence encoding coronaviridae replication signals, wherein said nucleotide sequence of said recombinant nucleic acid construct does not encode one or more functional coronaviridae proteins. Defective interfering coronaviridae virus-like particles produced from the recombinant nucleic acid construct are also disclosed along with methods of treating a subject having a corona virus infection using the virus-like particle.

The invention provides competitive particles, such as virus-like particles, RNAs and DNAs for the treatment or prevention of viral infections and methods of using such particles for treating or preventing or reducing the risk of viral infections (or symptoms thereof) in a subject, such as a human or animal subject. For example, the method herein is a method of reducing or reducing the establishment of a zoonotic population of a virus in an animal, such as a livestock or wild animal (eg, a bat, camelid or a Pholidota (eg, a pangolin)).

The present invention relates i.a. to a recombinant avian coronavirus spike protein or fragment thereof comprising a mutation at amino acid position 267 to Cysteine. Further, the present invention relates to an immunogenic composition comprising an avian coronavirus with such spike protein.