ID Second Half

RNA

Does the influenza virus contain DNA or RNA?

Negative

Influenze is an RNA virus. Does it contain positive or negative strands?

False

(True/False) Influenza viruses can synthesize proteins directly from the RNA they carry

False (only living)

(True/False) Viruses can perform replication in living and non-living cells

Obligate intracellular parasites

Viruses are also known as __________ ___________ ___________.

Hemagglutinin

this binds to the cells surface receptors, to allow the virus to enter the cell. Additionally, it takes place during the fusion process between the two membranes which ultimately releases the negative strand of RNA (uncoating)

Neuraminidase

This is an enzyme that helps release the virus from the membrane by binding to the sialic acid and allowing hydrolysis

RNA polymerase

Host cells cannot replicate viruses. Thus viruses have this which allow it to replicate on its own.

Inhibits influenza A and B neuraminidase (a transition state analog of sialic acid)

Oseltamivir MOA

True

(True/False) Oseltamivir is a pro-drug and becomes active after hydrolysis by esterase

Inhibits the initiation of the transcription of viral mRNA

Baloxavir MOA

Endonuclease

Baloxavir has an ______________ inhibitor which inhibits CAP-dependent influenza PA endonuclease (also described as the scissor)

CAP

What is necessary for viral mRNA's translation (modification found at 5' position of mRNA)

Cap Snatching Process

What process is described below:

Virus enters the cell and releases its RNA into the host cell’s nucleus (unusual for RNA viruses).

The virus’s RNA polymerase complex (which has a few subunits, like PA, PB1, PB2) goes to work:

PB2 binds to the 5' cap of a host cell’s mRNA.

The PA subunit acts like scissors and cuts off the cap along with a short stretch of nucleotides.

This snatched cap piece is attached to viral RNA, making it look like a normal host mRNA.

Now the host’s ribosomes read the viral RNA and make viral proteins — because it thinks it's an actual message.

uncoating

The addition of H+ ions into the M2 protein during influenza virus replication is an important step for the the later process of ___________ which ultimately leads to RNA replication.

Double Stranded DNA

What type of nuclei acid is carried by the Herpes viruses?

Varicella Zoster Virus

Which virus is responsible for chicken pox

Alpha Herpes Viruses

These viruses can result in disseminated disease involving several organs in neonates (CNS, lungs, skin, liver, eye, mouth) *transmitted at birth from mother

Ex: HSV-1/2, VZV

HSV-1

Which alpha herpes virus causes encephalitis in adults?

HSV-2

Which alpha herpes virus causes encephalitis in newborns

Beta-herpes virus

Cytomegalovirus is an example of this type of herpes virus - persists for life - cause Retinitis

Epstein-Barr Virus

Example of Gamma-herpes virus and causes mononucleosis syndrome in young adults

Increase absorption

Why do we have the 'ester' formation of Acyclovir

3

How many times does Acyclovir need to be phosphorylated

Viral Kinase TK

What enzyme performs the first phosphorylation in the MOA of Acyclovir

dGTP (deoxy-Guanosine-Tri-Phosphate)

Acyclovir is a competitor of what?

Acyclovir

Name the medication:

MOA = inhibits viral DNA polymerase and to lesser extent host DNA polymerase, competitor of dGTP, and incorporated into viral DNA and acts as chain terminator

HSV1 and HSV2 (VZV less common)

What are the indications for Acyclovir?

Nephro/neurotoxicities

What is the rare toxicities of Acyclovir when injected I.V.

True

(True/False) Valacylcovir has more nephro- and CNS- toxicities than Acyclovir

impaired production of viral thymidine kinase (most common - drug can not be activated)

What is the most common form of resistance for Acyclovir and Valacyclovir

Acyclovir/Valacyclovir

Altered TK substrate specificity or altered viral DNA polymerase are other Mechanisms of Resistance of which medication(s)?

B

Which of the following have a broader spectrum to treat herpes viruses?

A. Penicilovir/Famciclovir

B. Ganciclovir/Valganciclovir

Nucleotide

Cytidine is a ____________ analog

False (Already has phosphor group)

(True/False) Cidofovir requires phosphorylation by viral thymidine kinase

Cidofovir

Name the medication

MOA: phosphorylated to an active (tri)-phosphate form by cellular enzymes inhibits Viral DNA synthesis

- competitive inhibitor of viral DNA polymerase

- competes with dCTP

- Does only minimally inhibit host DNA polymerase

D

A 35-year-old man has developed genital herpes and is treated with valacyclovir. Despite the treatment, the symptoms do not disappear. A clinical analysis confirms that the virus is deficient in Thymidine Kinase. Which drug would you advise?

A. Acyclovir

B. Pencyclovir

C. Gancyclovir

D. Cidofovir

E. Another Drug

Cidofovir

Mechanism of resistance: mutations in viral DNA polymerase (30% patients after 3 month treatment)

Foscarnet

MOA:

- inhibits HSV DNA polymerase

- Binds to pyrophosphate binding site

- Inhibits cleavage of pyrophosphate from deoxynucleotide triphosphate

Nephrotoxicity, hypocalcemia, CNS effects

What are the adverse effects of Foscarnet?

Mutations in viral DNA polymerase

What is the mechanism of resistance of Foscarnet?

Docosanol

MOA: blocks fusion between the cellular membrane and viral envelope

only effective at early stages of the sore

Prevents re-infection

Topical Application

Abreva

What is the brand name of Docosanol?

Risk of infection, patients should be tested for TB, Higher risk of certain cancers (lymphoma)

Tocilizumab Black Box Warning:

Eyes (redness, pain, swelling) Skin rash, inflammation/swelling of the mouth, constipation

Toxilizumab most common adverse effects:

Heart attack/Stroke, Cancer, Blood Clots, death

Baricitinib Black Box Warning:

UTI, Upper respiratory infections, UTI, headache, acne, nausea, vomiting, etc.

Common side effects of Baricitinib

Targets RNA Dependent RNA polymerase (RdRp) of the virus

Remdesivir MOA:

True

(True/False) Remdesivir is a pro-drug

Paxlovid

Treatment of mild-to-moderate COVID-19 in adults who are high at risk for progression to severe COVID-19, including hospitalization and/or death, would be a great candidate for which medication?

Combination of nirmatrelvir (inhibits protease of virus) and ritonavir (inhibits CYP450s)

Paxlovid MOA:

Paxlovid

Changes in perception of taste is a common adverse effects of which drug?

Positive

The corona virus structure contains ___________ (positive/negative) sense RNA and envelope

RBD (Receptor Binding Protein)

SARS-CoV 2 fuses and enters the membrane by interaction with S1 (spike) glycoprotein w/ __________ on membrane receptors

Tocilizumab and Baricitinib

Which two Covid-19 treatment options reduce inflammation?

Remdesivir and Paxlovid

Which two Covid-19 treatment options reduce viral replication?

Tocilizumab

MOA: Binds to IL-6 receptor, resulting in suppression of IL-6 dependent signaling pathways, reduced expression of inflammatory cytokines and reduced immune response.

Baricitinib

MOA: Inhibits Janus Kinase (JAK) resulting in decreased transcription and translation of cytokines, and decreased immune response.

Polyene (Amphotericin B and Nystatin)

Ergosterile Binding Drugs

Azole and Allylamines

Ergosterol synthesis inhibitors

Disruption of Membrane structure by binding to ergosterile in fungal membranes

Amphotericin B MOA:

Nephrotoxicity

What is the serious adverse effects of Amphotericin B (Polyene)

C14-demethylase

Azoles and Triazoles target the _______________ to inhibit ergosterol synthesis

B (they modulate the activity of cytochrome P450s

Choose the most appropriate statement about anti-fungal azole drugs

A. They bind to ergosterol and destabilize the cell membrane of the fungi

B. They modulate the activity of cytochrome P450s

C. They inhibit the synthesis of mycolic acids

D. They inhibit the synthesis of peptidoglycan

Fluconazole

Drug Interaction Representative of Azoles

Terbinafine

Which Allylamine topical agent is prescribed as an oral medication for onychonmycosis of toe or finger nails

Inhibit synthesis of ergosterol by inhibiting the enzyme squalene epoxidase

MOA of Allylamines:

Inhibits the synthesis of the cell wall by inhibiting the 1, 3-beta glucan synthase

MOA of Micafungin:

Circular

Hepatitis B (chronic) main transmission is sex and the nucleic acid is ________________ (circular/linear) dble DNA

Linear

Hepatitis C (chronic) main transmission is sex and the nucleic acid is ______________ (circular/linear) RNA+

True

(True/False) Hepatitis B can be prevented by vaccination

Double strand DNA

Hepatitis B consists what? (RNA or DNA & Single or Double Strand)

monophosphate

Tenofovir is a Adenosine __________________ analog

Tenofovir

MOA: acts as a competitor for viral DNA polymerase and reverse transcriptase. It is also a chain terminator of viral DNA synthesis

True

(True/False) Tenofovir needs to be phosphorylated

Risk of Lactic Acidosis

What is the warning associated with Tenofovir

Interferon-a

MOA: stimulates cytotoxic activity of lymphocytes, natural killer cells and macrophages AND stimulates the expression of anti-viral enzymes that degrade RNAs and inhibit viral protein synthesis

Fever, Malaise, fatigue, muscle pain

30% of patients experience which flu-like symptoms while taking interferon-a

myelosuppression and cardiovascular effects

These two adverse affects may be experienced while taking Interferon-a at higher doses

subcutaneous injection

Interferon-a is usually given as a ________________ ______________ during weeks 48-52 of HBV treatment

False

(True/False) Complete cure of HBV can be attained

lifelong

Tenofovir and Lamivudine are nucleoside/nucleotide analogues that may require ______________ treatment of HBV

False

(True/False) Hepatitis C can be prevented with a vaccine

Direct-acting antiviral

What does DAA stand for in regard to therapy treatment for HepC?

Nucleotide

Is Sofosbuvir a Nucleoside or Nucleotide analog?

True

(True/False) Sofosbuvir is a pro-drug

Sofosbuvir

MOA: Inhibits HCV RNA polymerase

- Inhibits RNA replication by chain terminator

- Does NOT inhibit host RNA polymerase, DNA polymerase, or mitochondrial RNA polymerase

True

(True/False) Sofosbuvir has no effects on CYP P450s

unicellular

Protozoa are ______________ eukaryotes

Malaria

What is our focus example of blood protozoa (Plasmodium)

Toxoplasmosis

What is our focus example of tissue protozoa (Toxoplasma, Leishmania, Trypanosoma)?

Trichomoniasis

What is our focus example of Intestinal and vaginal protozoa (entamoeba, giardia, cryptosporidium, trichomona)

P. vivax and P. ovale

What are the two plasmodium species that reside "dormant" in the liver?

Fever and Chills

What are the two most common symptoms of Malaria?

Liver Stage

In the plasmodium life cycle, what is the initial replication stage?

Erythrocytic stage

What is the second stage of the plasmodium life cycle?

Phase in malaria during which infected red blood cells rupture, releasing merozoites and causing fever and chills.

True

(True/False) Gametocytes can only mature into a Gamete in mosquitos NOT humans

Artemisinin-based Combination Therapy

What does ACT, the standard treatment of Malaria, stand for?

Chloroquine

MOA: Accumulates in the digestive vacuoles of plasmodium

Inhibits Heme sequestration in vacuoles and hemozoin (polymerized heme) formation

Cardiovascular and Neurologic

What are the two severe adverse effects of Chloroquine when injected via I.V?