Final exam

virus

an infectious microbe consisting of a segment of nucleic acid (either DNA or RNA) surrounded by a protein coat; obligate intracellular parasites that rely on living cells to multiple

lytic cycle

method of viral reproduction that results in the destruction (lysis) of the host cell to release new viruses

lysogenic cycle

method of viral reproduction, where the virus integrates into the host genome

reverse transcriptase

an enzyme that synthesizes complementary DNA (cDNA) from an RNA template; essential for retroviruses to replicate

common human viruses

hepatitis B virus, human papillomavirus, human cytomegalovirus, human simplex virus, varicella-zoster virus, hepatitis C virus, respiratory syncytial virus

common zoonotic viruses

influenza and human immunodeficiency virus

bacteria; virus

the plague (Yersinia pestis) is a ________, not a _______

William Prusoff

American pharmacologist who developed the first antiviral drug, iodouridine; co-developed stavudine, an antiviral against HIV

5-substituted 2’-deoxyuridines

antiviral drugs that are non-functional analogs of 2-deoxyuridine; get incorporated into viral DNA replication and arrest base pairing, leading to viral replication inhibition

iodouridine

thymidine analog that is incorporated into viral DNA instead of thymidine, leading to non-functional, unstable viral proteins and DNA; type of 5-substituted 2’-deoxyuridine

trifluridine

a fluorinated pyrimidine nucleoside that gets incorporated into viral DNA, disrupting DNA synthesis and creating dysfunctional proteins; type of 5-substituted 2’-deoxyuridine

nucleoside and nucleotide analogs

synthetic compounds mimicking natural DNA/RNA building blocks; widely used as antiviral and anticancer agents

pyrophosphate analogs

compounds mimicking the structure of pyrophosphate, specifically designed to inhibit DNA polymerase and reverse transcriptase enzymes by blocking the pyrophosphate binding site

foscarnet

an antiviral drug that shows broad-spectrum activity against many viruses; type of pyrophosphate analog that binds to the pyrophosphate site of viral DNA polymerase

nucleoside reverse transcriptase inhibitors (NRTIs)

class of antiretroviral drugs used to treat HIV-1 and Hepatitis B; inhibit the reverse transcriptase enzyme, preventing viral RNA from converting into DNA; need to be phosphorylated to 5’-TP; act as chain terminators

non-nucleoside reverse transcriptase inhibitors (NNRTIs)

A class of antiretroviral drugs used to treat HIV-1 (not HIV-2) by binding to and disabling the reverse transcriptase enzyme; bind near the reverse transcriptase catalytic site and induce conformational changes that inhibit its function

protease inhibitors (PIs)

antiviral drugs that block the protease enzyme, preventing viruses like HIV and hepatitis C (HCV); have peptide-like scaffolds that allow them to bind to viral proteases and mimic the actual substrate, as a result inhibiting the function of viral proteases; administered with other drugs that enhance bioavailability and stability

integrase inhibitors (INSTIs)

highly effective antiretroviral drugs used to treat HIV by blocking the enzyme integrase, which prevents the virus from inserting its DNA into the host cell’s DNA, thus stopping replication

entry inhibitors

antiviral drugs that prevent viral entry to the host cell by blocking either membrane fusion, endocytosis, or genetic injection

biomimetic peptides (Enfuvirtide)

an HIV-1 fusion inhibitor; blocks virus-host membrane fusion

receptor antagonists (Maraviroc)

antiretroviral medication that blocks host cell surface receptors that interact with viral particles prior to entry

neutralizing antibodies (Palivizumab)

block viral receptor and prevent anchoring to the host cell

broad lipid-enveloped virus entry inhibitor (Docosanol)

antiviral that blocks viral entry to the cell; thought to interact with epithelial cell surface receptors

acyclic guanosine analogues

class of antiviral drugs that inhibit the viral DNA polymerase; prodrugs that require phosphorylation to then compete with the endogenous dGTP to bind and inhibit viral DNA polymerase

ganciclovir

a type of acyclic guanosine analog that is phosphorylated by host kinases

acyclovir and penciclovir

types of acyclic guanosine analogues that are phosphorylated by viral thymidine kinase

acyclic nucleoside (ANP) analogues

inhibit viral DNA polymerase and reverse transcriptases; mimic natural nucleotides, incorporating a stable phosphorus-carbon bond to bypass phosphorylation steps

HCV NS 5A/NS 5B inhibitors

antiviral drugs that when combined completely cures patients infected with certain HCV genotype

Hepatitis C virus (HCV) non-structural 5A (NS5A) protein

a protein crucial for viral RNA replication and particle assembly

NS5B

a critical RNA-dependent RNA polymerase

matrix 2 inhibitors

compounds that target matrix metalloproteinase-2, a zinc-dependent enzyme involved in collagen degradation and remodeling; includes amantadine and rimantadine

amantadine

first anti-influenza A drug approved; a type of matrix 2 inhibitor; blocks proton transport through the matrix 2 ion channel into the interior of viral particles, which is essential for viral uncoating within the endosomes

neuraminidase inhibitors (NAIs)

a class of antiviral drugs used to treat influenza; inhibit the neuraminidase surface glycoprotein, thus preventing the release of new viral particles from host cells; includes zanamivir, osteltamivir, peramivir, and laninamivir octanoate

favipiravir

a type of antiviral drug that inhibits RNA-dependent RNA polymerase

ribavirin

antiviral medication that works by inhibiting viral RNA synthesis; a guanosine analog

no

5-substituted 2’-deoxyuridines show ______ resistance in clinical settings

drug-target modification by amino acid substitutions

nucleoside and nucleotide analogs mechanism of resistance:

true

true or false: resistance to nucleoside reverse transcriptase inhibitors (NRTIs) develops through amino acids substitutions in the drug target

drug-target modification by amino acid substitutions

resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is mediated by:

true

true or false: protease inhibitors (Pis) have a high risk for developing resistance

drug-target modification by amino acid substitution and primary mutation (mild) followed by secondary mutation (strong)

mechanism of resistance to protease inhibitors:

drug-target modification by amino acid substitutions

mechanism of resistance to integrase inhibitors:

drug-target modification by amino acid substitutions

mechanism of resistance to entry inhibitors:

drug-target modification by amino acid substitutions

mechanism of resistance to acyclic guanosine analogous:

drug-target modification by amino acid substitutions, but DNA polymerase mutations reduce viral fitness

mechanisms of acyclic nucleoside phosphonate (ANP) analogues:

Strategic National Stockpile (SNS)

U.S. government’s primary repository of antibiotics, vaccines, antidotes, and medical supplies, designed to supplement state and local resources during public health emergencies; managed by Assistant Secretary for Preparedness and Response (ASPR)

drug-target modification by amino acid substitutions, but DNA polymerase mutations reduce viral fitness

mechanism of resistance to HCV NS 5A/NS 5B inhibitors:

drug-target modification by amino acid substitutions

mechanism of resistance to influenza virus inhibitors:

Coronavirus (CoV)

enveloped positive-strand RNA viruses that cause respiratory diseases ranging from the common cold to severe diseases like MERS, SARS, and COVID-19; includes 4 genera: alpha, beta, delta, and gamma

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

coronavirus that causes COVID-19; highly contagious and virulent; specificity is mediated by its receptors, angiotensin converting enzyme-2 (ACE-2) and transmembrane protease serine 2 (TMPRSS2)

lungs and small intestine

ACE-2 is predominantly expressed in the: