Antiviral Drugs

What types of drugs do viruses use?

Antiviral

What types of drugs do fungi use?

Antifungal

What type of drugs do bacteria use?

Antibiotics + Antibacterials

Nucleocapsid

Sounded by lipoprotein envelope, coat + nucleic acid core

What is the whole infective virus particle called?

Virion

Virus Composition

Nucleic Acids (RNA or DNA), capsid (protein coat that encloses nucleic acid), nucleocapsid

What do DNA viruses normally enter?

Host cell nucleus and direct the generation of new viruses

What does RNA retrovirus contain?

Reverse Transcriptase

Reverse Transcriptase

Makes a DNA copy of the viral RNA (the viral DNA copy is integrated into host cell genome and directs the generation of new virus particles)

What is the major challenge to effective antiviral treatment?

Development of resistance d/t viral mutations

How do antiviral drugs act by?

Inhibition of absorption (block viral entry), inhibiting of uncoating, inhibition of nucleic acid + protein synthesis, inhibition of viral maturation, inhibition of viral release

What antiviral drugs inhibition viral absorption?

Docosanol + Enfuvirtide

What antiviral drugs inhibit uncoating?

Amantadine + Rimantadine

What antiviral drugs inhibit nucleic acid and protein synthesis?

Ribavirin + Acyclovir + Ganciclovir + Efavirenz + Dolutegravir

What antiviral drugs inhibit viral release?

Zanamivir + Oseltamivir

Docosanol MOA

Inhibits fusion between the cell plasma membrane + HSV viral envelope (doesn’t affect replication + doesn’t promote resistance + doesn’t kill the virus)

Therapeutic Uses of Docosanol

HSV-1 (herpes labialis), available OTC

What antiviral drugs are used to treat Influenza A + B?

Amantadines + Neuraminidase Inhibitors

What is Amantadines also used in the management of?

Parkinson’s Disease

Amandatines MOA

Blocks penetration of influenza A (influenza B is now resistant), interferes with uncoating of virus and release of viral nucleic acid within host cell

Neuraminidase Inhibitors ”-Amivir” MOA

Prevent viral proliferation, should be taken within 30-36h and no later than 48h after flu-onset

What is RSV a common cause of?

Bronchiolitis + Pneumonia in children

Ribavirin MOA

Guanosine analogue that produces broad-spectrum activity against several RNA + DNA viruses

Ribavirin Therapeutic Use

Effective against RSV and used for severe viral pneumonia caused by RSV

Palivizumab

Monoclonal antibody indicated for prevention of RSV in neonates + young children (<2Y) with chronic lung disease

Black Box Warning of Ribavirin

Teratogenicity in pregnant females, children shouldn’t be in room when it is being administered

Acyclovir

Guanosine derivative, Valacyclovir is the prodrug

Acyclovir MOA

Triphosphate form by the viral thymidine kinase enzyme, inhibits viral DNA synthesis, resulting in reduced viral shedding + prevents formation of new lesions

What is the antiviral specific d/t in acyclovir?

D/t higher affinity for viral DNA polymerase

Side Effects of Acyclovir

Reversible nephrotoxicity, neurotoxicity, stinging sensations, N/V/D

Acyclovir Therapeutic Uses

First choice drug for HSV and VZV infection (oral formulation can be used during pregnancy)

Ganciclovir MOA

Inhibits viral DNA polymerase enzyme, phosphorylated in vivo to the triphosphate form

Side Effects of Ganciclovir

Infertility, embryotoxic, teratogenic, bone marrow suppression, more toxic than acyclovir

Therapeutic Uses of Ganciclovir

Used mainly for prevention + treatment of CMV infection

Which types of hepatitis can also cause chronic hepatitis?

Hepatitis B + C + D

Drugs Used in Combination for Hepatitis C

Ribavirin + Interferon Alpha + Protease Inhibitor

What type of interferon is used to treat hepatitis?

Interferon Alpha

Interferon Alpha MOA

Inhibits viral entry, synthesis of viral mRNAs and viral proteins, viral assembly + release (inhibits almost all steps of life cycle)

Adverse Effects of Interferon Alpha

Flu-like symptoms, neuropsychiatric effects (especially depression)

Ribavirin is used in combination with?

SubQ peginterferon alfa for treatment of chronic HCV

What combination is used for the management of Hepatitis B virus?

Interferon alpha + nucleoside analogues (combination achieves long-term viral suppression with reliably)

HIV Transmission Routes

Blood, unprotected anal sex, unprotected vaginal sex, breastmilk

CD4 Cells

WBC that fight infections, including HIV

Viral Load

Indicates quantity of HIV virus in blood

Drug-Resistance Test

Determines viable treatment options for strain of HIV

CD4 T-Cell Counts

Principal indicator of how much immunocompetence remains

Plasma HIV RNA (Viral Load) Assays

Ongoing treatment of HIV infection is guided primarily by monitoring viral load, which is determined by measuring HIV RNA in plasma

Diagnosis of AIDS

CD4 Count < 200

Undetectable HIV

Untransmittable

Enfuvirtide MOA

Prevents fusion of lipid bilayer of HIV with that of the host lipid bilayer

Therapeutic Use of Enfuvirtide

HIV-1 infection that is resistant to treatment (2x daily SQ injections, very expensive)

Zidovudine Drug Examples

Tenofovir disoproxil, tenofovir alafenamide, emtricitabine

Zidovudine MOA

Impair HIV replication by inhibiting reverse transcriptase enzyme necessary for conversion of viral RNA to viral DNA

Zidovudine (AZT) Side Effects

Lactic acidosis with hepatic steatosis, hepatomegaly, granulocytopenia, bone marrow suppression

What is a specific side effect of Tenofovir?

Osteoporosis

Efavirenz MOA

Binds directly to HIV-1 reverse transcriptase to block RNA and DNA-dependent DNA polymerase activity (resistance develops easily)

Efavirenz

First line drug in HIV therapy (only 1st line NNRTIs)

Efavirenz Side Effects

Flu-like symptoms, teratogenicity (considered category B)

Therapeutic Uses of Efavirenz

Always used with antiretroviral drugs to avoid resistance, compliance is critical to prevent NNRTI resistance

Dolutegravir MOA

Block retroviral integration of HIV DNA from being integrated into the nucleus of the host cell, thus stopping HIV replication

Dolutegravir Therapeutic Use

Most popular class for HIV d/t low resistance, minimal side effects, minimal drug-drug interactions

Lopinavir/Ritonavir

Effective, but limited use d/t side effects and increased resistance

Darunavir

Newer PI used for treatment of naïve patients (not to be used in sulfonamide allergies)

Lopinavir/Ritonavir MOA

Inhibit HIV protease enzyme that catalyzes synthesis of HIV proteins, thereby preventing synthesis + maturation of HIV

Lopinavir/Ritonavir Side Effects

Hyperglycemia/diabetes, altered fat redistribution, hyperlipidemia, osteoporosis

Therapeutic Uses of Lopinavir/Ritonavir

Used in combination with NRTIs, can reduce viral load to an undetectable level 

HAART

Highly Active Antiretroviral Therapy (aggressive, simultaneous use of at least 3 anti-HIV agents)

Advantage of HAART

Reduce viral load + prevent progression of HIV to AIDs (patient compliance improves outcome)

PrEP

Pre-Exposure Prophylaxis

PEP

Post-Exposure Prophylaxis

Injectable PrEP Medication

Cabotegravir which is administered every 2 months

PEP Medications

Should be given at least 72 hours after exposure (consists of 28-day course of 3-drug antiretroviral regimen)

FDA-Approved Treatment of COVID-19

Remdesivir, Olumiant, Actemra, Paxlovid