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.

The invention provides a method for determining whether a human immunodeficiency virus is resistant to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

The present invention relates i.a. to a 4/91 IBV (infectious bronchitis virus) encoding for a heterologous S (spike) protein or fragment thereof. Further, the present invention relates to an immunogenic composition comprising said 4/91 IBV encoding for a heterologous S (spike) protein or fragment thereof. Furthermore, the present invention relates to methods for immunizing a subject comprising administering to such subject the immunogenic composition of the present invention. Moreover, the present invention relates to methods of treating or preventing clinical signs caused by IBV in a subject of need, the method comprising administering to the subject a therapeutically effective amount of an immunogenic composition according to the present invention.

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.

The present invention aims to provide a new nucleic acid molecule for suppressing expression of the target gene, which (1) has a gene expression suppressing activity equivalent to or higher than that of siRNA, (2) shows no off-target effect of the sense strand, and (3) makes it possible to design a wider range of antisense strand sequences (extends the range of targetable sequences). Since the nucleic acid molecule of the following formula:

##STR00001##

wherein each symbol is as defined in the DESCRIPTION, has the superior properties of the above-mentioned (1) to (3), it is extremely useful as a novel gene expression inhibitor that replaces conventional siRNA.

A heat attenuated infectious bronchitis virus (IBV) isolate of PDRC DMV/1639 deposited at the ATCC under Patent Designation PTA-126757 and progeny and derivatives thereof and compositions thereof are presented. Methods for administering the isolates and compositions as vaccines to prevent virulent IBV infection in birds of the order Galliformes are also presented.

The present invention describes methods of generating a modified viral genome, producing infectious RNA, and generating modified viruses. The modified viral genome, infections RNA, and modified viruses comprise deoptimized nucleic acids; for example, codon-pair deoptimized or synonymous codon deoptimized. These modified viruses can be used in vaccines and methods of eliciting a protective immune response.

The present invention is directed to a nucleic acid suitable for use in treatment or prophylaxis of an infection with a coronavirus, preferably with a Coronavirus SARS-CoV-2, or a disorder related to such an infection, preferably COVID-19. The present invention is also directed to compositions, polypeptides, and vaccines. The compositions and vaccines preferably comprise at least one of said nucleic acid sequences, preferably nucleic acid sequences in association a lipid nanoparticle (LNP). The invention is also directed to first and second medical uses of the nucleic acid, the composition, the polypeptide, the combination, the vaccine, and the kit, and to methods of treating or preventing a coronavirus infection, preferably a Coronavirus infection.

The invention provides a method for determining whether a human immunodeficiency virus is resistant to a viral entry inhibitor. The methods are particularly useful for determining resistance to inhibitors that act by a non-competitive mechanism. In certain aspects, the methods comprise determining whether an HIV population is resistant to an HIV entry inhibitor, comprising determining a log-sigmoid inhibition curve comprising data points for entry of the HIV population in the presence of varying concentrations of the HIV entry inhibitor, wherein if the entry of the HIV population cannot be completely inhibited by the HIV entry inhibitor, the HIV population is resistant to the HIV entry inhibitor.

Attenuated isolates of the Arkansas serotype of infectious bronchitis virus (IBV), including the IBV isolate ArkGA p40 deposited at the ATCC under Patent Designation PTA-126834, and compositions thereof are presented. Methods for administering the isolates or compositions as vaccines to the prevent virulent IBV infection in birds of the order Galliformes are also presented.