2nd Antivirals

MOA of Antivirals

Prevent or eliminate one of the steps involved in the viral replicative cycle

Antiviral Drugs

• Have a limited use in veterinary medicine

• Mainly for the treatment of herpesvirus infections

• Topically for the treatment of ocular lesions

Antiviral Drugs

1. Species-specificity of viruses

2. Limited research and development of antiviral drugs for animals compared to humans

3. Priority for preventative measures in veterinary medicine, i.e., vaccination and biosecurity measures, for controlling viral diseases

4. Some animal viral infections can be zoonotic, thus, a need to be cautious with the use of antiviral drugs in animals to avoid the development of resistance and potential transmission to humans

5. Off-label use of antiviral drugs should be done with caution and often requires specific dosage adjustments

Idoxuridine

Trifluridine

• Mainly active against DNA viruses such as herpesvirus and poxvirus

• Both are commercially available as topical ophthalmic preparations for the treatment of herpetic keratitis

• Idoxuridine

• 1 week

• Trifluridine

Due to the high cost, ______ should be used initially, and if no response is seen within _____, _______ therapy should be initiated.

Cytarabine

• Used as an antineoplastic agent in dogs and cats for treatment of leukemia and lymphoma

• Causes bone marrow suppression, which limits its use as an anti-viral agent

Vidarabine

• Used topically in the treatment of herpes keratitis

• Less potent against feline herpesviruses than idoxuridine or trifluridine

Ribavirin

• Its strongest antiviral activity is against RNA respiratory viruses (influenza A and B) and herpes viruses

• Myxoviruses, paramyxoviruses, arenaviruses, bunyaviruses, retroviruses, adenoviruses, and poxviruses

• Aerosolized is preferred for treating susceptible respiratory infections

Acyclovir

• Used as a treatment for equine herpesvirus encephalitis

• The equine herpesvirus type 1 (EHV-1)

  • Causes myeloencephalopathy, respiratory disease, abortion, and neonatal infections

Famciclovir

Used to treat herpesvirus-1 ( FHV-1) associated disease in cats

Valacyclovir

Absorbed as the prodrug → Converted to the active drug—acyclovir—in the patient

Zidovudine

• More commonly known as AZT

• The use of AZT has been investigated in cats as a clinical therapy for Feline Immunodeficiency Virus (FIV)

  • How is FIV spread?

  • The primary mode of transmission is through bite wounds

AZT

Zidovudine is commonly known as?

AZT / Zidovudine

Shown to reduce clinical signs when given to two FIV-positive cats at a dose of 10 mg/kg twice a day subcutaneously for a period of 3 weeks

Foscarnet

• It inhibits DNA and RNA polymerases and reverse transcriptase

• Viruses inhibited include avian myeloblastosis, Moloney murine leukemia, Rauscher leukemia, influenza, bovine leukemia, African swine fever, baboon endogenous virus, simian sarcoma, human herpes, and human immunodeficiency viruses

Amantadine and Rimantadine

• Effective in the prevention of respiratory infections caused by influenza A virus but not as effective as vaccination

• Have been used to treat flu outbreaks, resulting in shorter duration fever and more rapid resolution of symptoms

• Its use in poultry is thought to be responsible for the amantadine- resistant influenza strains seen in the Chinese avian flu pandemic in 2005

Rimantadine

Shows greater promise as an antiviral drug in horses

Amantadine

• Used for the treatment of pain syndromes in animals

• Proposed MOA: inhibition of the neurotransmitter N- methyl-D-aspartate (NMDA)

Interferon

• Potent cytokines

• Anti-viral

• Immunomodulating

• Anticxncxr properties

Interferon

• Licensed for use in the treatment of viral disease in dogs and cats in Japan and other countries

• Used in feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) in cats, and bovine viral diarrhea (BVD) in cattle.

• Used as part of the treatment regimen to help boost the immune response and aid in the recovery of dogs canine parvovirus infection

L-Lysine

An essential amino acid that blocks the availability of arginine that is necessary for the replication of herpesviruses

L-Lysine

• May also be efficacious in cases of herpesvirus keratitis in cats

• A prophylactic dose of 500 mg 6 hours prior to viral challenge, and then continued at 500 mg PO q12h decreased the severity of the ocular lesions in cats compared to controls

Summary of Antivirals

• Idoxuridine & Trifluridine

  • DNA virus 

  • herpes-, pox-

  • commercially available as topical ophthalmic

  • herpetic keratitis

• Cytarabine

  • antineoplastic agent

  • leukemia & lymphoma

  • bone marrow suppression

  • limited use as anti-viral agent

• Vidarabine

  • topical — herpes keratitis

  • less potent against feline herpesvirus than I&F

• Ribavirin

  • aerosolized pref. for susceptible resp. infections

  • strongest antiviral activity against RNA respiratory virus and herpes virus

  • myxo-, paramyxo-, arena-, bunya-, retro-, adeno-, pox-

• Acyclovir

  • equine herpesvirus encephalitis

  • EHV-1

• Famciclovir

  • FHV-1 

• Valacyclovir

  • prodrug -> Acyclovir

• Zidovudine

  • AZT

  • FIV

• Foscarnet

  • Inhibits DNA & RNA polymerases and reverse transcriptase

• Amantadine & Rimantidine

  • prevent resp. infec. by influenza A virus

• Amantadine

  • poultry — resistance 

  • treatment of pain syndromes

  • inhibits NMDA

• Rimantidine

  • better in horses 

• Interferon

  • potent cytokines

  • antiviral

  • immunomodulating

  • anticxncxr properties

  • FeLV

  • FIV

  • BVD

  • aid in CPV

• L-lysine

  • essential amino acid 

  • blocks availability of arginine

  • herpesvirus

  • herpesvirus keratitis