Methods for increasing the survival of aquatic and other animals exposed to an aquatic virus, birnavirus or other RNA virus and compositions for such methods

#1. Field of the Invention

#The present invention is directed generally to treating organisms, particularly aquatic organisms susceptible to a virus, such as an aquatic birnavirus infection, by administering compounds that increase the survival the subjects when exposed to or infected with an virus. The invention is directed to a prophylactic/therapeutic method for increasing the survival of aquatic species, particularly fish populations, that may be or are infected with a virus such as an aquatic birnavirus, and more particularly to a composition for the prevention and treatment of infectious pancreatic necrosis virus (IPNV) in fish comprising isoxazol compounds and/or aminoglycoside compounds. The invention is also directed to a prophylactic/therapeutic method for increasing the survival of animal species, particularly poultry and pig populations, that may be or are infected with a virus such as a birnavirus, ortomixovirus, picornavirus and to a composition for the prevention and treatment of infectious bursal disease virus (IBDV) in poultry comprising isoxazol compounds and/or aminoglycoside compounds.

#2. Background

#FIG. 1 is an autoradiograph showing the effect of acivicin on IPNV genomic RNA synthesis. Monolayers of CHSE-214 cells were infected with IPNV either in the absence (lanes 1 and 4) of acivicin, or the presence of acivicin at 25 μg/ml (lanes 2 and 5) or the presence of acivicin at 70 μg/ml (lanes 3 and 6). Simultaneously, acivicin and 50 μCi/ml of [32P]-orthophosphoric acid were added at 0 hours post-infection (h.p.i.) and the cells were incubated at 15° C. At 24 hours post-infection (lanes 1, 2, and 3) and 48 hours post-infection (lanes 4, 5, and 6), the cells were harvested, RNA extracted therefrom, and analyzed by 7% polyacrylamide gel electrophoresis (PAGE) and autoradiography. The migration of the A and B segments of the IPNV genomic RNA is indicated by arrows.

#FIG. 2 is an autoradiograph showing the effect of acivicin on IPNV polypeptide synthesis. Monolayers of CHSE-214 cells were infected with IPNV either in the absence (lanes 1 and 9) or presence of acivicin at 25 μg/ml (lanes 4 and 10) or in the presence of acivicin at 70 μg/ml (lanes 5 and 11). Acivicin was added at the time of infection (zero h.p.i.) and the cells were incubated at 15° C. Six hours post-infection, a 50 μCi/ml of [35S]-methionine was applied to the cells. At 24 h.p.i. (lanes 1 through 5) and at 48 h.p.i., 100 μl of a protein disruption solution was added to the cell monolayers. The polypeptides from the disrupted cells were analyzed by 15% SDS-PAGE and autoradiography. The non infected cell samples were also included in lanes 2, 3, 6, 7, and 8. The migration of IPNV polypeptides is indicated.

#FIGS. 3A and 3B are autoradiographs showing the effect of acivicin on IPNV particle formation.

#The instant invention addresses a long standing need in aquaculture and animal production by providing a method of administering isoxazol and/or aminoglycoside compounds to aquatic and other animals susceptible to infection from a virus, particularly RNA viruses, selected from the group consisting of: IPNV, IBDV, pillar cell necrosis virus (PCNV), infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia virus (VHSV), infectious hypodermal and hematopoietic necrosis virus (IHHNV), shrimp white spot virus (WSV), Taura syndrome virus (TSV), hepatopancreatic parvovirus (HPV), infectious salmon anemia virus (ISAV), tellina virus, oyster virus, a Birnaviridae virus, a Rhabdoviridae virus, an Iridoviridae virus, a Reoviridae virus, a Picornaviridae virus, and an Ortomixoviridae virus, in a manner that increases the survival of the animals. The term “animal(s)” includes living species in the animal kingdom, including aquatic animals and, therefore, is not limited to mammals.

#The terms “administer” or “administered” or “administration” indicate any means by which the prophylactic/therapeutic compound is delivered to the animal so that the compound is available to block viral replication or entry. Such delivery means include, but are not limited to: introduction into the aquatic environment; inclusion in the food; and injection into the aquatic animal, such as intraperitoneal injection. Methods of administration also include: bathing the aquatic animals in tanks containing the compound; and inclusion of the compound in food. The method of the invention and the administering can be performed before, during, or after IPNV or IBDV exposure and/or infection. Further, the method can be conducted before, during, and/or after IPNV or IBDV infection as well as before, during and/or after IPNV or IBDV illness or death appears. For example, administration can be initiated after infection when 20% mortality is observed.

#Administration includes those protocols that increase survival of an aquatic animal exposed to IPNV. Administration also includes those protocols that increase survival of an animal exposed to IBDV. Administration can occur before, during and/or after viral exposure. Such protocols include, but are not limited to the following: (a) inclusion of the antiviral compound in at least one daily feeding; (b) inclusion of the antiviral compound in the aquatic environment for at least 0.5-2.0 hours/day on a daily or cyclical schedule that includes, but is not limited to: biweekly, tri-weekly, and one-week-on/one-week-off; (c) administration prior to: the presence of viral titers, IPNV exposure, IPN illness, and/or IPNV-associated deaths; (d) administration upon detection of: the presence of viral titers, IPNV exposure, IPN-illness, and/or IPNV-associated deaths; (e) administration following: the presence of viral titers, IPNV exposure, IPN illness, and/or IPNV-associated deaths; (f) the protocols described herein; (g) daily administration for periods from about 5 days to about 30 days; and/or (h) administration for more than one time per day. Such protocols also include, but are not limited to the following: (a) administration prior to: the presence of viral titers, IBDV exposure, IBDV illness, and/or IBDV-associated deaths; (b) administration upon detection of: the presence of viral titers, IBDV exposure, IBDV-illness, and/or IBDV-associated deaths; (c) administration following: the presence of viral titers, IBDV exposure, IBDV illness, and/or IBDV-associated deaths; (d) the protocols described herein; and/or (g) daily administration for periods from about 5 days to about 30 days.