Antiviral Medication

See Also

Mechanism

Viruses lack the easy targets of Antibiotics (e.g. cell membranes, peptidoglycan cell walls, ribosomes)
Viruses have only a few potential targets for Antivirals
1. Viral capsid (Protein coat)
2. Nucleic Acids
3. Enzymes for replication
Most Antivirals target replication steps
1. Results in virustatic agents that suppress replication, but do not kill the virus
2. Viable virus remains in latent state
Most common Antiviral mechanism is as Nucleotide analogues
1. Act as non-functional decoys competitively binding viral replication enzymes
2. Some are incorporated into DNA, resulting in non-functional enzyme Proteins

Medications
Herpesvirus Antivirals - Nucleic Acid Polymerase Inhibitors (DNA or RNA)

See Herpesviridae
See Herpes Simplex Virus (HSV)
See Varicella Zoster Virus (VZV)
See Cytomegalovirus (CMV)
Synthetic Nucleoside analogues (e.g. Acyclovir, Famciclovir, Valacyclovir, Ganciclovir)
1. Acyclovir, Famciclovir, Valacyclovir are indicated for Varicella Zoster Virus and Herpes Simplex Virus Infections
2. Ganciclovir and Valgancyclovir have greater activity against CMV and EBV (used in AIDS and BMT patients)
3. Agents are prodrugs metabolized by multiple enzymes (esp. thymidine kinase) to active triphosphate drug
  1. These prodrugs require thymidine kinase for actvity
  2. Famciclovir and Valacyclovir reach higher drug levels after oral ingestion than Acyclovir
  3. Famciclovir and Valacyclovir lack the protential nephrotoxicity of IV Acyclovir
4. Thymidine kinase phosphorylates these prodrugs into their active form
  1. Thymidine kinase is found in Herpesviridae, but not in humans
    1. Acyclovir, Famciclovir and Valacyclovir are only active only when Herpes viruses are present
  2. Some strains of CMV do not carry Thymidine kinase
    1. Results in Antiviral resistance
Pyrophosphate analog - DNA Polymerase Inhibitor (e.g. Foscarnet)
1. Foscarnet is a synthetic analog of inorganic pyrophosphate
2. Selectively blocks viral DNA Polymerases at their pyrophosphate binding site, preventing DNA Replication
3. Indicated in CMV Retinitis and HSV infection in Immunocompromised patients
Phosphonate Nucleoside analog - DNA Polymerase Inhibitor (e.g. Cidofovir)
1. Active against the Herpes Family of Viruses, especially Cytomegalovirus (CMV).
2. Synthetic, acyclic, monophosphate Nucleotide analog of deoxycytidine (deoxyribonucleoside in DNA synthesis)
3. Cidofovir is activated within infected host cells, via phosphorylation by pyruvate kinases to Cidofovir diphosphate
  1. Cidofovir diphosphate competes with deoxycytosine-5-triphosphate (dCTP) for viral DNA Polymerase
  2. When incorporated into DNA, it prevents viral DNA polymerization, blocking viral DNA Replication

Medications
HIV Antiviral Agents

See Anti-Retroviral Therapy
See HIV Pathophysiology
Host Cell fusion and penetration inhibitors
1. Fusion Inhibitors (e.g. Enfuvirtide)
  1. Blocks HIV fusion to cell anchor Proteins
2. CCR5 Inhibitors (Maraviroc)
  1. Block HIV binding at CCR5 co-receptor
  2. CD4 Coreceptors (CCR5 or CXCR4) must be present on the host cell surface for HIV penetration
Nucleic Acid Polymerase Inhibitors (DNA or RNA)
1. Nucleoside Reverse Transcriptase Inhibitor (nRTI, e.g. Tenofovir, Emtricitabine, Lamivudine, Zidovudine)
  1. Anti-Retroviral Therapy for HIV Infection
2. Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI, e.g. Efavirenz, Nevirapine, Doravirine, Etravirine, Rilpivirine)
  1. Anti-Retroviral Therapy for HIV Infection
Protease Inhibitors (e.g. Atazanavir, Darunavir, Fosamprenavir, Indinavir, Ritonavir, Saquinavir)
Integrase Inhibitors (e.g. Bictegravir, Cabotegravir, Dolutegravir, Raltegravir)
1. Anti-Retroviral Therapy for HIV Infection

Medications
Other Antiviral Agents

Additional Antivirals are targeted at the infected host cell factors
Nucleic Acid Polymerase Inhibitors (DNA or RNA)
1. NS5B Polymerase Inhibitors (e.g. Sofosbuvir) or NS5A Inhibitors (e.g. Velpatasvir)
  1. Hepatitis C Antiviral Regimen
2. RdRP polymerase Inhibitor (e.g. Remdesivir)
  1. Covid19
  2. Viral Hemorrhagic Fever (e.g. Ebola Virus, Marburg Hemorrhagic Fever)
Protease Inhibitors (e.g. Atazanavir, Darunavir, Fosamprenavir, Indinavir, Ritonavir, Saquinavir)
Neuraminidase Inhibitor (e.g. Oseltamivir)
1. Influenza Infection

References