Antiviral Pharmacology

True or false: Many antivirals offer broad coverage of viruses

False

Explain the fundamental molecular events that occur in cells to convert DNA to protein.

DNA replication, DNA transcription to RNA, RNA translation to protein

True or false: Reverse transcription and RNA replication are processes that take place in our human cells

False, these are characteristics of viral cells

What drug is most useful against primary HSV1/2 and is associated with significant reduction in shedding, symptoms, and recovery times?

Acyclovir

What is the mechanism of action of Acyclovir?

Acyclovir is phosphorylated by the infected HSV cell, and is then trapped and accumulates in the infected cell, then the phosphorylated acyclovir competes with endogenous nucleotides to inhibit viral DNA polymerase and acts as a chain terminator in viral DNA synthesis (OVERALL INHIBITS DNA SYNTHESIS)

What is the spectrum of activity for Acyclovir used to treat HSV1/HSV2 recurrence?

Prophylactic use reduces duration

What is the spectrum of activity of Acyclovir used within 24h of rash onset with VZV?

Reduces lesions and duration

What is the spectrum of activity of Acyclovir with shingles (herpes zoster)?

Reduces pain and healing times

What is the nucleotide analog of Acyclovir (already phosphorylated) used IV for treatment of CMV retinitis in HIV+ patients that increases the time to progression of CMV retinitis and has been used in ACV resistance HSV infections?

Cidofovir

What is present on the outside of the cell membrane that allows Hemagglutinin of RNA viruses to stick to the cell membrane?

Sialic acid

What drug is an anti-influenza agent that inhibits influenza A and B RNA polymerase complex, preventing synthesis of viral proteins?

Baloxavir

True or false: Baloxavir has to be used prophylactically or within 48 hr of symptom onset

True

What anti-influenza agent is a neuraminidase inhibitor that inhibits virus release from infected cells and has prophylactic use?

Oseltamivir

What class of drugs mimics sialic acid and thus inhibits virus release and new infection?

Neuraminidase inhibitors

True or false: Combination drugs targeting two HepC proteins required for replication are highly effective therapeutics

True

What anti-SARS drug is a prodrug that inhibits RNA-dependent RNA polymerase?

Remdesivir

What anti-SARS drug combination inhibits the SARS protease that is required and inhibits CYP3A4 to boost therapeutic concentration?

Nirmatrelvir-Ritonavir

True or false: Long-lived T-cells harboring latent HIV DNA integrated into host chromosomes can be targeted by anti-retrovirals

False

True or false: Antiretrovirals can prevent virus transmission to fetus in HIV+ pregnant women

True

Why is drug resistance with HIV a significant problem?

HIV has a high mutation rate and monotherapy promotes emergence of resistance viruses

What drug blocks the binding of the HIV outer envelope protein gp120 to the CCR5 chemokine receptor (chemokine receptor antagonist)?

Maraviroc

What drug binds to the HIV envelope protein gp41 and inhibits gp41-mediated fusion of the virus envelope with the cell membrane?

Enfuvirtide

What is the only approved parenteral HIV drug?

Enfuvirtide

What is the main adverse effect of Enfuvirtide?

Cyst development at injection site

What occurs when RNA-dependent DNA polymerase copies viral RNA into proviral DNA for integration into host cell chromosome?

Reverse transcriptase

What major adverse effect of NRTIs can be caused due to an inhibited mitochondrial DNA polymerase?

Myopathy

What drugs bind hydrophobic pocket distinct from the active site in HIV reverse transcriptase and induces a change that reduces enzyme activity?

Non-Nucleoside RT inhibitors (NNRTIs)

What drug is a Non-Nucleoside RT inhibitor?

Efavirenz

What drugs are HIV integrase inhibitors that prevent virus integration into host chromosome?

Cabotegravir and Dolutegravir

What drug is a competitive inhibitor of HIV protease and prevents proteolytic cleavage of HIV precursor polyproteins, preventing maturation of virus to infectious form?

Ritonavir

Why is monotherapy for HIV problematic and never used?

Resistance develops due to very frequent mutation of viral genome

What is the first line treatment for Highly Active Anti-Retroviral Therapy?

Dolutegravir/Lamivudine OR Integrase inhibitor/NRTI

What should begin early in pregnancy to achieve zero detectable virus in the fetus?

Three drug combinations