The present invention relates to in silico methods for identifying compounds which decrease or prevent the binding of the viral RNA-dependent RNA polymerase from the Orthomyxoviridae family or variant thereof, to its ligand, (preferably to cellular Pol II, more preferably to CTD), as well as methods of producing the identified compounds. The present invention also relates to a compounds identifiable and/or producible by said methods. The present invention also relates to antibodies directed against the binding site of the RNA-dependent RNA polymerase, to its ligand (in particular to cellular Pol II, in particular to CTD of Pol II) as well as nucleic acids encoding said antibodies and vectors comprising the nucleic acid. The present invention relates to a pharmaceutical composition producible according to said method, and/or comprising said compound, said antibody, said nucleic acid, or said vector. The present invention also relates to the use of said compound, said antibody, said nucleic acid, said vector or said pharmaceutical in treating, ameliorating, or preventing disease conditions caused by viral infections with viruses of the Orthomyxoviridae family.

The disclosure provides methods and compositions useful for obtaining induced stem cells, methods of making and use thereof.

Provided herein are attenuated influenza viruses and methods of making attenuated influenza viruses.

The disclosure provides compositions, methods of treatment, and methods of making and using compositions to deliver a nucleic acid to a subject. Methods of using the compositions as a COVID-19 vaccine for the treatment of a coronavirus infection are also provided.

The application relates to the technical field of biomedicine, in particular to a limited self-replicating mRNA molecular system, producing method and use. The limited self-replicating mRNA molecular system including: a first mRNA encoding a mutated alphavirus replicase; and at least one second mRNA encoding a target protein; by generating specific mutation adjustments in the nsP2 subunit of mutated replicase, this limited self-replicating mRNA molecular system can achieve limited self-replication and avoid cytotoxicity; by constructing different mRNA with mutated alphavirus replicase and different target proteins, the mutated alphavirus replicase encoded by the first mRNA can simultaneously replicate multiple different target proteins, achieving sustained expression of multiple target proteins.

Immunogenic compositions and methods of their use in eliciting immune responses to coronaviruses, such as SARS-CoV-2 are provided.

The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.

The present invention relates to a retrovirus packaging cell which expresses a temperature sensitive RNA-dependent-RNA polymerase (RdRp).

The present invention provides a method for identifying a substance capable of inhibiting at least one activity of an RNA-dependent RNA polymerase (RdRp) comprised in an influenza viral ribonucleoprotein (RNP) complex, which method comprises or consists of: (a) providing an aqueous suspension of purified influenza virus comprising said RNP complex; (b) adding to said suspension of step (a) (i) a nonionic or zwitterionic surfactant; and (ii) a reducing agent; (c) incubating the mixture obtained in step (b) in order to obtain an influenza virus lysate; (d) contacting the influenza virus lysate obtained in step (c) with a test substance under conditions that permit said test substance to interact with said RdRp comprised in said RNP complex, said RNP complex being present in said influenza virus lysate; and (e) determining whether said test substance inhibits said at least one activity of said RdRp.

The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.