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JP-2026076345-A - Azelastine as an antiviral treatment

JP2026076345AJP 2026076345 AJP2026076345 AJP 2026076345AJP-2026076345-A

Abstract

[Problem] To provide novel antiviral treatments, pharmaceutical products, and chemical products that can be used to prevent viral infection and/or viral spread in subjects who have been exposed to, infected with, or are at risk of viral infection. [Solution] An azelastine compound in an antivirally effective amount for use as an antiviral substance in a pharmaceutical formulation. [Selection Diagram] None

Inventors

  • ナギ，エスター
  • ナギ，ガボール
  • シヤルト，バレリア
  • コンラット，ロベルト

Assignees

  • ツェビナ・ゲーエムベーハー

Dates

Publication Date
20260511
Application Date
20260218
Priority Date
20200529

Claims (20)

  1. Azelastine compounds in an antivirally effective amount for use as antiviral substances in pharmaceutical formulations for use in preventive or therapeutic treatment of subjects requiring antiviral treatment.
  2. a) Coronaviruses (β-coronaviruses such as SARS-CoV-2, MERS-CoV, SARS-CoV-1, HCoV-OC43, HCoV-HKU1; or α-coronaviruses such as HCoV-NL63, HCoV-229E, or PEDV, and naturally occurring variants or offshoots of any of the aforementioned viruses); b) Adenoviridae (adenoviruses or human adenoviruses, such as HAdVB, HAdVC, or HAdVD); c) Paramyxoviridae (RSV or human RSV, e.g., hRSV subtype A or B); or d) Orthomyxoviridae (influenza virus or human influenza virus, preferably influenza virus A (IVA) such as H1N1, H3N3, or H5N1, or influenza virus B (IVB), or influenza virus C (IVC), or influenza virus D (IVD)). An azelastine compound for use according to claim 1, which treats a disease condition caused by or associated with infection by one or more viruses selected from among.
  3. One or more different coronaviruses are naturally occurring SARS-CoV-2 mutants or variants, such as SARS-CoV-2 mutants or variants containing one or more mutations in the SARS-CoV-2 S-protein, preferably K417N, L452R, N501Y, D614G, P681H, P681R, E484K, E484Q, or 69/70 deletion in SEQ ID NO: 4, and preferably the SARS-CoV-2 mutant or variant is selected from the group consisting of B. 1.1.7 (UK mutant), B. 1.351 (South Africa), P. 1 (Brazil), B. 1.617 (India), and B. 1.618 (Bengal) variants, as described in claim 2.
  4. An azelastine compound for use according to any one of claims 1 to 3, wherein the pharmaceutical preparation is a medical product or drug comprising an azelastine compound and a pharmaceutically acceptable carrier.
  5. An azelastine compound for use according to any one of claims 1 to 4, wherein the disease condition is a common cold, nasal or sinusitis, pharyngeal and laryngeal infection, bronchiolitis, diarrhea, skin rash, or pneumonia, acute respiratory spurt syndrome (ARDS).
  6. An azelastine compound for use according to any one of claims 1 to 5, wherein the antiviral effective dose is effective in preventing infection of virus-susceptible cells and thereby treating the disease state.
  7. An azelastine compound for use according to any one of claims 1 to 5, wherein the antiviral effective dose is 0.1 to 500 μg/dose.
  8. An azelastine compound for use according to any one of claims 1 to 7, wherein the pharmaceutical formulation is formulated for topical administration, preferably for use in the upper or lower respiratory tract, nasal cavity, lungs, oral cavity, eyeball, or skin, or for systemic administration by intravenous, intramuscular, subcutaneous, intradermal, transdermal, or oral administration.
  9. An azelastine compound for use according to any one of claims 1 to 8, wherein the pharmaceutical formulation is administered to a subject as a spray, powder, gel, ointment, cream, foam, or liquid solution, lotion, mouthwash, aerosolized powder, aerosolized liquid, granules, capsule, drop, tablet, syrup, lozenge, eye drop, or formulation for injection or injection.
  10. The azelastine compound for use according to any one of claims 1 to 9, wherein the azelastine compound is applied to the target nose in an antiviral effective dose of 1 to 1000 μg per nostril.
  11. The azelastine compound for use according to any one of claims 1 to 10, wherein the azelastine compound is administered as the sole antiviral agent, or the treatment is combined with a further treatment using one or more active substances selected from the group consisting of antiviral agents, anti-inflammatory agents, and antibiotics.
  12. An azelastine compound for use according to any one of claims 1 to 11, to be used to treat subjects infected with or at risk of becoming infected with a virus, preferably humans, dogs, cats, horses, camels, cattle, or pigs.
  13. Azelastine compounds for use as antiviral substances in medical products to treat biological surfaces to prevent viral infection and/or virus spread.
  14. The azelastine compound for use according to claim 13, wherein the biological surface is a mucous membrane surface that is infected with or at risk of being infected with one or more different viruses.
  15. The azelastine compound for use according to claim 14, wherein one or more different viruses are preferably beta-coronaviruses such as SARS-CoV-2, MERS-CoV, SARS-CoV-1, HCoV-OC43, or HCoV-HKU1; or alpha-coronaviruses such as HCoV-NL63, HCoV-229E, or PEDV; and coronaviruses of the Coronaviridae family selected from the group consisting of naturally occurring variants or mutants of any of the aforementioned viruses.
  16. One or more different coronaviruses are naturally occurring SARS-CoV-2 mutants or variants, such as SARS-CoV-2 mutants or variants containing one or more mutations in the SARS-CoV-2 S-protein, preferably K417N, L452R, N501Y, D614G, P681H, P681R, E484K, E484Q, or 69/70 deletion in SEQ ID NO: 4, and preferably the SARS-CoV-2 mutant is selected from the group consisting of B. 1.1.7 (UK mutant), B. 1.351 (South Africa), P. 1 (Brazil), B. 1.617 (India), and B. 1.618 (Bengal) variants, as described in claim 15.
  17. An azelastine compound for use according to any one of claims 13 to 16, wherein the medical product is formulated for topical use, preferably for application to the upper or lower respiratory tract, nasal cavity, lungs, oral cavity, eyeball, or skin.
  18. An azelastine compound for use according to any one of claims 13 to 17, wherein the medical product is used as a solution, dispersion, dry powder, or aerosolized liquid or powder.
  19. The azelastine compound for use according to any one of claims 13 to 18, wherein the azelastine compound is applied in an antiviral effective amount, preferably in an amount of 1 ng to 1000 ng/ cm² .
  20. Use of azelastine compounds as antiviral agents.

Description

This invention relates to novel uses of antihistamine compounds for treating viral infections, particularly methods and compounds for treating coronavirus infections (e.g., SARS virus or MERS virus), adenovirus infections, human respiratory multinuclear virus infections, and influenza infections. Coronaviruses are single-stranded RNA viruses with a diameter of approximately 120 nanometers. Coronaviruses are prone to mutation and recombination, and are therefore highly diverse. There are approximately 40 different variants, which primarily infect humans, non-human mammals, and birds. These variants are present in bats and wild birds and can spread to other animals, and thus to humans. Based on their genome structure, there are four main genera (alpha, beta, gamma, and delta coronaviruses). Alpha- and beta coronaviruses infect only mammals, typically causing respiratory symptoms in humans and gastroenteritis in other animals. As of December 2019, only six different coronaviruses were known to infect humans. Four of these (HCV-NL63, HCV-229E, HCV-OC43, and HKU1) typically cause mild, cold-like symptoms in immunocompetent humans, while the remaining two have caused pandemics over the past two decades. In 2002-2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused the SARS epidemic, resulting in a 10% mortality rate. Similarly, Middle East respiratory syndrome coronavirus (MERS-CoV) caused a pandemic in 2012 with a 37% mortality rate. In the latter half of 2019 and the first half of 2020, a novel coronavirus, SARS-CoV-2, was discovered to be closely related to SARS-CoV and was the cause of a large-scale, rapidly spreading respiratory illness, including pneumonia. Since the recognition of this novel coronavirus, the disease it causes has been called coronavirus infection 2019 (COVID-19). SARS-related coronaviruses are coated with a spike protein containing a variable receptor-binding domain (RBD). This RBD binds to angiotensin-converting enzyme-2 (ACE-2) receptors found in the heart, lungs, kidneys, and gastrointestinal tract, thereby facilitating viral entry into target cells. The initial virus strain that spread from Wuhan was considered a "wild-type" virus, and this virus quickly gave rise to mutant strains, i.e., variants that evolved through natural selection based on higher infectivity. In early March 2020, a mutant strain with a D614G mutation in the spike protein (B.1 mutant) was identified in Europe, and this mutant strain quickly replaced the initial Wuhan strain globally. Subsequently, SARS-CoV-2 mutant strains B.1.1.7 (also known as 20I/501Y.V1, VOC 202012/01) and B.1.351 (also known as 20H/501Y.V2) were identified in the UK and South Africa, respectively, and have since spread to many countries. These mutant strains have a variety of mutations in the gene encoding the spike protein. One of these mutations is located at position 501 of the receptor-binding domain (RBD that binds to human ACE2), where the amino acid asparagine (N) is replaced with tyrosine (Y) (mutation N501Y). The B. 1.1.7 mutant also has several other mutations, including a 69/70 deletion that likely results in a conformational change of the spike protein, and P681H near the S1/S2 furin cleavage site. The combination of these mutations results in higher receptor binding, more efficient diffusion, and higher pathogenicity compared to the first version that appeared in Wuhan, China in 2019. The B. 1.351 mutant also has E484K and K417N mutations in addition to N501Y, but lacks the 69/70 deletion. Several pieces of evidence suggest that this mutant emerged due to immunosuppression, i.e., as a means of escaping the human immune response resulting from natural infection or active immunity acquisition using passive immunization therapy or different vaccines. The E484K mutation is thought to be responsible for the reduced vaccine effectiveness. This mutation (along with 16 other mutations, N501Y and K417T) was also detected in the Brazilian variant, which was named P. 1. Variant P. 1 caused widespread infection in Brazil and was later detected worldwide. This variant is suspected to cause more severe illness and a higher mortality rate in relatively younger individuals and to evade the immune response induced by previous variants and some vaccines. Variant B. 1.617 was first detected and spread in India. This variant has 13 mutations, including three mutations of concern regarding immune evasion: E484Q, L452R, and P681R. Lineage B. 1.618 has become one of the dominant variants in West Bengal and possesses two amino acid deletions (H146del and Y145del), as well as E484K and D614G mutations in the spike protein. This lineage is suspected to be more infective and pose a threat that evades natural or vaccine-induced immunity. Widespread vaccination is highly likely to induce the emergence of further mutant strains with different combinations of currently known mutations and new mutations. Accelerated global vaccination, along with