M5 Antiviral Agents Practice Flashcards

A collection of 70 vocabulary flashcards covering viral structure, drug mechanisms, and specific antiviral agents based on the PMOC 311 lecture.

Virus (Living characteristics)

Characteristics including reproduction at a fantastic rate in host cells and the ability to mutate.

Virus (Nonliving characteristics)

Characteristics including being acellular, carrying out no independent metabolism, and possessing DNA or RNA but never both.

Viral size range

Viruses range from $20$ to $14,000\,nm$ in length as ascertained by electron microscopy.

Virion

An intact infectious viral particle consisting of a Genome, Capsid, and Envelope.

Genome

The internal genetic material of a virion, containing either DNA or RNA.

Capsid

The protein shell of a virus.

Envelope

The outer layer covering the capsid in some viruses.

DNA-dependent DNA polymerase

A viral enzyme target specifically found in DNA viruses.

RNA-dependent RNA polymerase

A viral enzyme target specifically found in RNA viruses.

RNA-dependent DNA polymerase (RT)

A viral enzyme target found in retroviruses, also known as reverse transcriptase.

Viral Enzyme Targets (Retrovirus)

Includes Proteases, Integrase, and Reverse Transcriptase.

Neuraminidase

A viral enzyme target found in orthomyxoviruses.

Entry Inhibitors

A class of antiviral drugs that includes fusion inhibitors and CCR5 receptor antagonists.

Inhibition of uncoating

The mechanism of action for the drugs Rimantadine and Amantadine.

Inhibition of RNA synthesis

The mechanism of action for Interferon and Ribavirin.

Inhibition of genome replication

A mechanism achieved by inhibiting DNA polymerase or RT virus using Nucleoside/Nucleotide analogs or Non-nucleoside RTI.

Acyclovir, AZT, and Lamivudine

Examples of Nucleoside or Nucleotide analogs used to inhibit genome replication.

Inhibition of viral assembly

The mechanism of action for Proteases Inhibitors.

Inhibition of viral release

The mechanism of action for Neuraminidase inhibitors.

Amantadine ($1966$)

Known as $1$-adamantanamine hydrochloride (Symmetrel); used for Influenza A.

Rimantadine ($1993$)

Known as $\alpha$-methyl-$1$-adamantane methylamine hydrochloride (Flumadine).

Influenza A Seasonal Prophylaxis

The use of Amantadine and Rimantadine, which is $70-90\%$ effective.

M2 protein

An integral membrane protein functioning as an ion channel; the main biochemical locus of action for Influenza type A virus inhibitors.

Neuraminidase Inhibitors

Drugs such as Zanamivir (Relenza) and Oseltamivir (Tamiflu) effective for both influenza type A and B.

Oseltamivir (Tamiflu)

A neuraminidase inhibitor specifically mentioned as effective for $H5N1$.

Interferon Types

Includes $IFN-\alpha$, $IFN-\beta$, and $IFN-\gamma$.

Interferon broad spectrum activity

Mediated through inhibition of viral penetration/uncoating, mRNA synthesis, translation of proteins, and viral assembly/release.

Indications for Recombinant $IFN-\alpha$ and $IFN-\beta$

Venereal warts, Chronic hepatitis B and C, Kaposi sarcoma, and Multiple sclerosis.

Idoxuridine (Stoxil, Herplex)

Introduced in $1963$; an iodinated analog of uridine used for herpes simplex keratitis.

Idoxuridine Mechanism

Inhibitor of viral DNA polymerase, causing inhibition of viral DNA synthesis.

Cytarabine

A Pyrimidine (cytidine) nucleoside drug for shingles and herpetic keratitis that blocks deoxycytidine utilization.

Trifluridine (Viroptic)

A trifluorinated analog of thymidine indicated for $HSV-1$ and $HSV-2$ primary keratoconjunctivitis.

Trifluridine Monophosphate

An irreversible inhibitor of thymidylate synthetase.

Trifluridine Triphosphate

Competitively inhibits thymidine triphosphate incorporation into DNA by DNA polymerase.

Vidarabine (Vira-A)

Obtained by fermentation with strains of Streptomyces antibioticus; active against herpresvirus and poxvirus.

Vidarabine Target Spectrum

Antiviral action is completely confined to DNA viruses.

Vidarabine mechanism

Phosphorylated to a triphosphate which competes with deoxyadenosine triphosphate for viral DNA polymerase and acts as a chain terminator.

Acyclovir

An acyclic guanosine derivative used against $HSV-1$, $HSV-2$, VZV, EBV, and CMV.

Acyclovir Adverse Reactions

Occasional GI upset, dizziness, headache, lethargy, and joint pain.

Valacyclovir Hydrochloride (Valtrex)

The L-valyl ester of acyclovir; a prodrug intended to increase bioavailability by increasing lipophilicity.

Valacyclovir pharmacokinetics

Achieves serum levels $3$ to $5$ times greater than those achieved with oral acyclovir.

Ganciclovir (Cytovene)

A hydroxymethyl analog of acyclovir with greatly enhanced activity against CMV infection.

Ganciclovir Limitations

Associated with myelosuppression and is mutagenic, carcinogenic, and teratogenic.

Penciclovir and Famciclovir

Acyclic guanine nucleoside analogs that inhibit viral DNA synthesis; penciclovir is first phosphorylated by viral thymidine kinase.

Cidofovir (Vistide)

(S)-$3$-hydroxy-$2$-phosphonomethoxypropyl cytosine; acts as an antimetabolite to deoxycytosine triphosphate (dCTP).

Cidofovir Mechanism

Competitive inhibitor of viral DNA polymerase that causes DNA chain termination.

Foscarnet

Inorganic pyrophosphate compound that inhibits viral DNA polymerase and HIV RT directly without activation by phosphorylation.

Foscarnet Metal Binding

Described as an excellent ligand for metal ion binding; noted for being nephrotoxic.

Zidovudine (AZT)

A Deoxythymidine analog synthesized in $1978$ by Lin and Prusoff that acts as a chain terminator.

Zidovudine Elimination

Eliminated primarily by renal excretion following glucuronidation in the liver.

Zidovudine Adverse Drug Reactions (ADR)

Myelosuppression leading to anemia or neutropenia, GI intolerance, headache, and insomnia.

Didanosine (Videx)

A synthetic analog of deoxyadenosine (ddATP) that inhibits RT and acts synergistically with AZT.

Didanosine (Videx) Toxicity

Causes painful peripheral neuropathy and pancreatitis (nausea, abdominal pain, elevated amylase).

Zalcitabine

A cytosine analog (ddCTP) with a long intracellular half-life ($t_{1/2}$) of $10\,hrs$ used against $HIV-1$ and $HIV-2$.

Stavudine

Unsaturated pyrimidine nucleoside bioactivated to a triphosphate; has a high oral bioavailability of $86\%$.

Stavudine ADR

Dose-limiting toxicity is a dose-related peripheral sensory neuropathy.

Lamivudine

A Cytosine analog used for $HIV-1$ and chronic hepatitis B with oral bioavailability exceeding $80\%$.

Ribavirin

A guanosine analogue with D-Ribose that interferes with the synthesis of guanosine triphosphate and inhibits capping of viral mRNA.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Agents like Nevirapine, Delaviridine, and Efavirenz that bind to an allosteric site on viral reverse transcriptase.

NNRTIs Resistance

Rapid emergence of resistance prohibits monotherapy; there is common cross-resistance among this class.

NNRTIs ADR

Skin rash.

Protease Inhibitors (PIs)

Drugs like Ritonavir, Nelfinavir, Saquinavir, and Indinavir that prevent splitting of viral precursor polypeptides.

Protease Inhibitors Synergy

Combination therapy is recommended to avoid emergence of resistance due to genotypic alterations.

Syndrome of altered body-fat distribution

An ADR of PIs characterized by Buffalo Hump, Truncal Obesity, facial atrophy, and Peripheral Atrophy.

Lopinavir

The first PI approved for patients as young as $6\,months$; typically used in combination with Ritonavir.

Ritonavir-Lopinavir Interaction

Ritonavir inhibits Lopinavir metabolism by $CYP3A4$, causing higher levels of Lopinavir in the system.

Integrase Inhibitors

Drugs that prevent viral DNA from merging with T cell DNA, including Raltegravir ($2007$) and Dolutegravir ($2013$).

Remdesivir

First FDA-approved COVID treatment ($2020$); inhibits RNA polymerase in patients weighing at least $88\,pounds$.

Remdesivir Cost

Approximately $\$520/vial$ (private) or $\$390/vial$ (government).

TRUVADA for PrEP® ($2004$)

Pre-Exposure Prophylaxis containing Tenofovir disoproxil fumarate and emtricitabine to reduce HIV-$1$ risk from intercourse.