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JP-7856771-B2 - Antiviral compositions comprising nucleic acid-derived nucleoside analogs and pharmaceutically acceptable salts thereof.

JP7856771B2JP 7856771 B2JP7856771 B2JP 7856771B2JP-7856771-B2

Inventors

  • ムン，ホ・ジン
  • キム，ヨン・ナム
  • イ，ナ‐ラ
  • イ，チャンソク
  • チョ，ア・ルム

Assignees

  • シージェイ チェイルジェダン コーポレーション

Dates

Publication Date
20260511
Application Date
20221222
Priority Date
20211222

Claims (8)

  1. A composition for use in inhibiting viral infection, comprising one or more nucleoside analogs selected from the group consisting of nucleoside analogs of chemical formulas 1 to 6 below and pharmaceutically acceptable salts thereof , The aforementioned viruses include Porcine Reproductive and Respiratory Syndrome virus (PRRSV), Porcine Epidemic Diarrhea virus (PEDV), Swine Influenza virus (SIV), Avian Influenza virus (AIV), Porcine Rotavirus (PRV), Porcine Circovirus (PCV), and Infectious Bronchitis Virus (Infectious Bronchitis Virus). A composition comprising one or more viruses selected from the group consisting of (IbV), Newcastle disease virus (NDV), Bovine viral diarrhea virus (BVDV), Bovine rotavirus (BRV), and Canine parvovirus (CPV) .
  2. The composition according to claim 1 , characterized in that it is a pharmaceutical composition or a food composition.
  3. A feed additive for use in inhibiting viral infection, comprising one or more nucleoside analogs selected from the group consisting of nucleoside analogs of chemical formulas 1 to 6 below and pharmaceutically acceptable salts thereof , The aforementioned viruses include Porcine Reproductive and Respiratory Syndrome virus (PRRSV), Porcine Epidemic Diarrhea virus (PEDV), Swine Influenza virus (SIV), Avian Influenza virus (AIV), Porcine Rotavirus (PRV), Porcine Circovirus (PCV), and Infectious Bronchitis Virus (Infectious Bronchitis Virus). A feed additive containing one or more viruses selected from the group consisting of *Various viruses* (IBV), avian Newcastle disease virus (NDV), bovine viral diarrhea virus (BVDV), bovine rotavirus (BRV), and canine parvovirus (CPV) .
  4. The feed additive according to claim 3 , which is for use with mammals, birds, fish, or arthropods.
  5. A feed for use in inhibiting viral infection , comprising one or more nucleoside analogs selected from the group consisting of nucleoside analogs of chemical formulas 1 to 6 below and pharmaceutically acceptable salts thereof, The aforementioned viruses include Porcine Reproductive and Respiratory Syndrome virus (PRRSV), Porcine Epidemic Diarrhea virus (PEDV), Swine Influenza virus (SIV), Avian Influenza virus (AIV), Porcine Rotavirus (PRV), Porcine Circovirus (PCV), and Infectious Bronchitis Virus (Infectious Bronchitis Virus). Feed containing one or more viruses selected from the group consisting of (IbV), Newcastle disease virus (NDV), Bovine viral diarrhea virus (BVDV), Bovine rotavirus (BRV), and Canine parvovirus (CPV) .
  6. The feed according to claim 5 , which is for mammals, birds, fish, or arthropods.
  7. A method for inhibiting viral infection, The process involves administering the composition described in claim 1 to a non-human subject, The aforementioned viruses include Porcine Reproductive and Respiratory Syndrome virus (PRRSV), Porcine Epidemic Diarrhea virus (PEDV), Swine Influenza virus (SIV), Avian Influenza virus (AIV), Porcine Rotavirus (PRV), Porcine Circovirus (PCV), and Infectious Bronchitis Virus (Infectious Bronchitis Virus). A method comprising one or more viruses selected from the group consisting of (IbV), Newcastle disease virus (NDV), Bovine viral diarrhea virus (BVDV), Bovine rotavirus (BRV), and Canine parvovirus (CPV) .
  8. The method according to claim 7 , wherein the non-human subject is a mammal, bird, fish, or arthropod.

Description

This application relates to antiviral compositions, immunomodulatory compositions, and feed compositions comprising nucleic acid-derived nucleoside analogs and pharmaceutically acceptable salts thereof. Globally, the damage caused by viral diseases to humans and animals is steadily increasing, and the scale of the damage is also tending to become enormous. The significant impact on humanity from zoonotic viruses such as SARS-CoV-2, MERS, and influenza (Influenza), which have emerged or persisted in recent years, as well as the social and economic damage caused by animal viruses such as avian influenza and African swine fever, are further urging the development of effective measures to control viral diseases. In particular, there is no doubt that complete control of viral diseases is impossible, especially given that only a few vaccines are currently available as the sole means of combating viruses. Efforts to develop animal virus treatments as a powerful solution to this problem have continued for decades. Research continues into viral therapeutics (inhibitors of viral infection and replication) to control many animal viruses, such as influenza viruses like porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV), swine influenza virus (SIV), or avian influenza virus (AIV), porcine rotavirus (PRV), porcine circovirus (PCV), avian infectious bronchitis virus (IBV), avian Newcastle disease virus (NDV), bovine viral diarrhea (BVD), bovine rotavirus (BRV), and canine parvovirus (CPV). (Kim et al., 2013 Virus Res. 171(1):44-53, Paul C Jordan et al., 2018 Antivir Chem Chemother. 26:1-19, Andrea J) (Pruijssers et al., 2019 Current Opinion in Virology 35:57-62) Currently, highly effective antiviral drugs have not yet been commercialized, and given the significant threat posed by viral diseases, there is a very high need for the development and commercialization of antiviral agents. Kim et al. , 2013 Virus Res. 171(1):44-53Paul C. Jordan et al. , 2018 Antivir Chem Chemother. 26:1-19Andrea J Prijssers et al. , 2019 Current Opinion in Virology 35:57-62 This diagram shows how IMP, XMP, and GMP are converted to dialdehyde forms to obtain the structures of the dialdehyde nucleosides of chemical formulas 1 to 3 according to this application.The chemical structures of the nucleosides of chemical formulas 4-6 according to this application are shown, obtained by converting IMP, XMP, and GMP to acyclic diol forms, respectively.The image above shows the anti-PRRSV efficacy of inosine in the form of dialdehyde, as confirmed by immunofluorescence staining, and the image below shows the PRRSV infection rate using this efficacy.The image above shows the anti-PRRSV efficacy of xanthosine in the form of dialdehyde, as confirmed by immunofluorescence staining, and the image below shows the PRRSV infection rate using this efficacy.The image above shows the anti-PRRSV efficacy of guanosine in dialdehyde form, as confirmed by immunofluorescence staining, and the image below shows the PRRSV infection rate using this efficacy.The image above shows the anti-PRRSV efficacy of acyclic diol inosine, confirmed by immunofluorescence staining, and the image below shows a graph illustrating the PRRSV infection rate using this efficacy.The image above shows the anti-PRRSV efficacy of acyclic diol xanthosine, confirmed by immunofluorescence staining, and the image below shows the PRRSV infection rate using this efficacy.The image above shows the anti-PRRSV efficacy of acyclic diol guanosine, confirmed by immunofluorescence staining, and the image below shows the PRRSV infection rate using this efficacy.This shows the blood concentration of xanthosine in dialdehyde form, measured over time, after administration via oral (intragic) and IP (intraperitoneal) injection.This shows the blood concentration of guanosine in dialdehyde form, measured over time, after administration via oral (intragic) and IP (intraperitoneal) injection.This shows the schedule for the influenza virus challenge test using mice.This shows the changes in body weight of mice in each group during the 7-day monitoring period after SIV infection.This shows the changes in survival rates of mice in each group during the 7-day monitoring period after SIV infection.This is the result of observing lesions in lung tissue excised through autopsies on days 3, 5, and 7 after SIV infection, separately for each group.The results of measuring the viral titer remaining in lung tissue extracted through autopsies on days 3, 5, and 7 after SIV infection, using the PCR method, are shown for each group.These are photographs of lung tissue lesions representative of each group, taken at the final autopsy seven days after SIV infection.This shows the schedule for the PRRS virus challenge test using piglets.This shows the weight changes of piglets in each group during the 14-day monitoring period after PRRSV infection.This is a comparison of the viral load in l