Antivirals Flashcards
Antivirals
Facts
- Can’t grow easily in culture
- Limited to no animal models (req by FDA)
- Some can be dangerous to study (require a biosaftey level 4 lab)
- Compound interfering w/ viral growth can negatively affect the host cell
– If target nucleic acid synthesis, it will affect human enzyme, processes
— Lead to side effects
Antiviral
Facts II
- Compound needs to completely inhibit virus (not just partial inhibition)
– Otherwise mutation and resistance - Many infections are acute, short duration
– Antiviral need to be given early - No broad-spectrum antiviral agen available
- Rapid diagnostic test have been limited
General Principles
Most agents used to treat viral infections either
- Directly inactivate viruses (virucides)
- Inhibit viral replication at the cellular levels (antivirals)
- Augment or modify the host reponse to infection (immunomodulators)
Some treatment destroys host tissue and virus simultaneously
- Cryotherapy or laser for warts
- Only for some mucocutaneous infections
Primary Prevention (best)
- Immunization
- Antiviral for prophylaxis
Pharmacotherapy for Viruses Vs. Bacteria
At times treat based on symptoms with no identification
- Although sometimes the case with bacterial infections
- Some viral infections do not have effective treatments
– Supportive care
— Common cold medication (treat symptoms: fever, cough, runny nose)
— Antiseizure, fluids, antipyretics (acetaminophen) for some central nervous system infections
CICLOVIR, CYCLOVIR
Therapeutic indications
Herpes Simplex Virus (HSV):
- Herpes labialis (cold sores)
- Genital herpes (STD/STI)
- Keratitis (eye), encephalitis (brain)
Varicella-Zoster Virus (VZV)
- Varicella virus (chickenpox)
- Herpes-zoster virus (shingles)
HSV and VZV travel along the nerve path
Applications for Drugs with… everything
Active Against Herpesviruses
Human cytomegalovirus (HCMV, CMV)
- Retinitis
- Can affect other organs
- Many exposed but usually doesn’t cause disease; opportunistic infection in
immunocompromised
Ganciclovier (IV; powder) good for transplant rejection
MANTADINE, AMIVIR
Application
Influenza
- Burden of flu: Influenza A > B
- Influenza A virus (a lot of genetic diversity)
- Influenza B
- Genetic changes
- Antiviral can moderatly speed time to resolution, reduce severity in hospitalized patients
- Antiviral sometimes used to prevent or ameliorate disease in those exposed
FLOVIR, CAVIR, VUDINE
Application
Treatment of Hepatitis B Virus (HBV)
- Chronic infection
- Cirrhosis
- 25% develop hepatocellular cancer
- Most asymptomatic
PREVIR, BUVIR, ASVIR
Application
Hepatitis C Virus (HCV)
- Bimodal distribution)
- Cause of liver transplants, Cirrhosis
Genotypes
- 6 genotypes
Direct Acting Antivirals (DAAs)
Revolutionized HCV treatment: Protease inhibitors were first
- Boceprevir: oral(tablet)
- Telaprevir: Oral(tablet)
NS5B polymerase inhibitors
Sofosbuvir (Oral Tablet Sovaldi®)
Dasabuvir (Oral Tablet)
NS5A inhibitors
Daclatasvir
Elbasvir
Ombitasvir
Pibrentasvir
Velpatasvir
All are oral tablet
NS3/4A protease inhibitors
Glecaprevir
Paritaprevir
Simeprevir
Voxilaprevir
All are oral tablet
Combination products
BUVIR, ASVIR, PREVIR (plus VIRIN
and FERON)
- Ombitasvir/Paritaprevir/Ritonavir Technivie® (genotype:4)
- Elbasvir/Grazoprevir Zepatier® (genotype1,4)
- Sofusbuvir/Velpatasvir/Voxilaprevir Vosevi® (genotype1,2,3,4,5,6)
SIVIR, TRELVIR, PIRAVIR
Applications
Covid-19
- SARS-CoV-2
- Mutation continue to emerge (variant, subvariant)
Antiviral can:
- Speed time to resolution
- Reduce severity
- decrease healthcare system burden
- Increased benefit in ≥65 yo, risk factors
