Lesson 3 Flashcards
Viral infections in humans and animals are preferably controlled by _______. However, when a vaccine is not available, example for those major viral diseases or emergence of a new virulent strain of virus, antiviral chemotherapy is necessary. Since, viruses are obligate intracellular parasites, development and delivery of antiviral therapy present many challenges relating to efficacy and toxicity for the host. In addition, the efficacy of antiviral chemotherapy is further complicated by viral latency (ex: herpesviruses). The other limiting factor in antiviral chemotherapy is the development of resistance.
Effective antiviral drugs inhibit virus-specific events related to virus replication; from preventing virus entry into host cells, interfering with uncoating, genome replication or assembly to release of virus from host cells (Table 1).
immunization
Classes of antiviral drugs
- Immunomodulators
- Ion-channel blocking compounds
- Neuraminadase inhibitors
- Antiviral drugs which inhibit viral genome replication
- Non-nucleoside polymerase inhibitors
- Protease inhibitors
: enhance innate immune responses, indirect antiviral effects by inducing cytokines prominently interferons.
Immunomodulators
: mediate the early immune responses to viral infections
Type 1 interferons
a) Type 1 interferons : mediate the early immune responses to viral infections, major examples:
i. Interferon-α (IFN-α): produced by mononuclear phagocytes ii. Interferon-β (IFN-β): produced by fibroblasts and other cells
b) Type 2 interferon : or interferon-Ɣ (IFN-Ɣ) is produced by stimulated T cells and NK cells. It activates macrophages and thereby contribute to the initiation of specific antiviral resistance mediated by antibodies and T lymphocytes.
c) Example of immunostimulating drugs to viral infections: Imiquimod and Inosine pranobex
: produced by mononuclear phagocytes ii. Interferon-β (IFN-β): produced by fibroblasts and other cells
Interferon-α (IFN-α)
: or interferon-Ɣ (IFN-Ɣ) is produced by stimulated T cells and NK cells. It activates macrophages and thereby contribute to the initiation of specific antiviral resistance mediated by antibodies and T lymphocytes.
Type 2 interferon
Example of immunostimulating drugs to viral infections:
Imiquimod and Inosine pranobexp
: prevents virus uncoating shortly after endocytosis of virus by the host cell (
Ion-channel blocking compounds
- Ion-channel blocking compounds: prevents virus uncoating shortly after endocytosis of virus by the host cell (Fig.1).
a) Example:
Amantadine
- has antiviral activity against influenza A virus by inhibiting an early step in the replication of the virus. Briefly, the presence of amantadine interfere with the ion channel function of the M2 protein in the nucleocapsid of the virus thus inhibits acid-mediated dissociation of the ribonucleoprotein complex early in replication, a process essential for uncoating of the single-stranded RNA genome.
Amantadine
: interfere with release of virus from host cells
Neuraminadase inhibitors
is required to cleave sialic acid from the cell membrane of the budding virions. Otherwise, persisting sialic acid residues on newly released adjacent virions causes aggregation of the virions on the cell surface.
Neuraminidase
- Neuraminadase inhibitors: interfere with release of virus from host cells (Fig. 1). Neuraminidase is required to cleave sialic acid from the cell membrane of the budding virions. Otherwise, persisting sialic acid residues on newly released adjacent virions causes aggregation of the virions on the cell surface.
a) Example:
Oseltamivir and Zanamivir (anti-influenza drugs)
Oseltamivir and Zanamivir (anti-influenza drugs) process
Most of these drugs are nucleoside analogues which inhibit viral polymerases, especially DNA polymerases, by competing with natural substrates and incorporate into the growing DNA chain where they often terminate elongation.
Antiviral drugs which inhibit viral genome replication
- Antiviral drugs which inhibit viral genome replication: Most of these drugs are nucleoside analogues which inhibit viral polymerases, especially DNA polymerases, by competing with natural substrates and incorporate into the growing DNA chain where they often terminate elongation.
a) Example:
Nucleoside analogue drugs
Thymidine analogue
Nucleoside analogue drugs such as;
Note : memorize the function
i. Acyclovir: used against herpesvirus
ii. Famciclovir: has inhibitory activity against herpesviruses, poxviruses, papillomaviruses and adenoviruses
iii. Penciclovir: used against herpesvirus iv. Ganciclovir: active against cytomegalovirus v. Ribavirin: anti-influenza drug
Thymidine analogue
Note: function
i. Idoxuridine: Ophthalmic solutions containing idoxuridine are used for treating herpesvirus keratitis in animals
inhibit replication of viruses by binding to the pyrophosphate binding site of the DNA polymerase to block binding of nucleotides.
Non-nucleoside polymerase inhibitors
- Non-nucleoside polymerase inhibitors: inhibit replication of viruses by binding to the pyrophosphate binding site of the DNA polymerase to block binding of nucleotides.
a) Example:
Foscarnet (against herpesvirus, HIV, hepatitis B virus)
used against HIV proteasesp
Protease inhibitors:
Resistance to anti-viral drugs
Since most antiviral compounds are highly selective and usually target a specific viral protein, viruses can readily become resistant through point mutations in the virus genome which often limits the usefulness of antiviral drugs.
Development of resistance, a multifactorial process, may involve the selection and use of the antiviral compounds, drug concentration at the site of infection, initial virus susceptibility to the treatment, inherent characteristics of the invading virus and the immune status of the host.
