antiviral med chem AND brand/gens

which hep is infectious

hep A virus

which hep is serum bep

hep B

which hep is post-transfusion hep

hep C

what is enterically transmitted form of hep

hep E virus

what are tumor causing viruses

ebv, papilloma viruses, hbv, kaposisi’s scarmoa herpesvirus, adult t-cell leukemia virsues, hcv

antiviral drug design is …

hard lol

• antigenic shift + drift

• latent period— hard to tell whats going on

what are the drugs used for flu

amantadiine— inhibits uncoating so you dont get rna in cell

oseltamivir— (neuraminidase inhib) HA sticks to virus host cell, NA cleaves sialic acid so that virus cannot be released from the cell to go infect other ones

baloxavir— stops “cap snatching” so the virus cannot take over cell mRNA

what does amantadine look like /waht do

for flu

inhibitrs penetration of RNA virus particles into host cell by stopping uncoating

what are the neuraminidase inhibitors ? what look like? what for?

Oseltamivir (Tamiflu), Zanamivir, Peramivir— for the flu

• virons cannot be released to spread to other cells

which flu class is good for proph and shortens recovery time

keeps spread from mkaing it worse OR from spreading enough to infect you

which NA inhib is the only po acitve one

oseltamivir

which NA inhib is a prodrug ? what hydrolyzes it

oseltamivir

• esterases

what does carboxyl at c2 do for NA inhibitrs (sar)

importnat to binding, must be hydrolyzed for acitivty

what are the four groups importnat for binding in NA inhibitors for flu

A carboxyl at C2 •

A basic group at C4 (amino or guanidine) •

N-acetyl at C5 •

R at C6

what strucutre at c-6 of NA inhibitors for flu gives best bidnign

3-pentyloxy

brand name for the cap-depend inhibitor for flu?

xofluza (gen Baloxavir marboxil)

is Baloxavir marboxil a prodrug

YES the acid is active

how does Baloxavir marboxil work

blocks endonucleases of the flu virus that stop “cap snatching,” st viral mRNA cant be made (normally made by hijacking the cell mRNA)

Baloxavir marboxil what group important to binding the Mn in active site? what is counseling consequence of this?

where acid forms.

• this gorup also binds dietary cations— antacids, dairy, ca, fe, etc

how are all teh hsv, vzv, and cmv things similar?

they are all nucleotide/side related

• these are all the herpes viruses

how are all hsv/hzv/cmv agents taht are prodrugs get activated

phospohrylation

how acyclovir work/look

lacks a 3’-oh so you can’t continue the chain. looks like guanine

why acyclovir sleective

viral thymidine kinase (TK).is a specific enzyme to herpes viruses that activates teh drug

what is big ad eff of acyclorvir

nephrotox— drink plenty of water bc can form crystals

• lowk not water soluble

how is valacyclovir dif than acyclovir

has a valine lol. makes it a prodrug which increases bioavailablity PO

what is the deal with Ribavirin

broad spec of antiviral, just nucleoSide (no phosphate), not effective

what is nucleoside vs tide

side is just base and sugar

tide has the phosates

what is a nonnucleoside analoguue? adv?

foscarnet. no activate

• binds viral DNA polymerase directly

what are some NS5a inhibitors (for herpes)?

Ledipasvir

Velpatasvir

Daclatasvir

Elbasvir

Pibrentasvir

what do ns5a inhib do (herpves, such as ledipasvir, velpatasvir, etc)

big “butterfly” like molecule

• prevent protein complex assembly— RNA replication, etc

what are the polymerase inhibitors ? whawt they do?

Sofosbuvir and dasabuvir

• viral RNA-dependent RNA polymerase

• anti-hepatitis

what is HIV life cycle

• attachment

• fusion

• reverse transcription

• integration

• protein synth

• protease cleave/maturation

• infectious virion

what are entry inhibitors for hiv? what do?

• prevents fusion of hiv-1 viral envelope with host plasma membrane

  • enfuvirtide, maraviroc

how Enfuvirtide work and what for

binds gp 41 to block fusion of HIV of cell membrane

Maraviroc how work

ccr5 antagonist— blocks co-receptor binding to allow hiv-1 to get into cells

is sofosbuvir for hepitisits a prodrug

yes that whole bit starting from the N on the phosphate gets left

Enfuvirtide (the gp41 entry inhibitor for hiv) what look like

linear 36 amino acid synth peptide

• prevenets confirmational change of fusion of viral and cell membranes

how does maraviroc (entry inhibitor that stops ccr5 receptor) work

small molecule antagonist

• blocks inx between human ccr5 and hiv-1 gp120— stops hiv-1 from entering into cells

• for this specific pehnotype of HIV-1 as well (ccR5-tropic)

how do NRTI work (nucleoside/tide reverse transcriptase inhibitor)

gives reverse transcriptase of HIV the wrong building blocks

why we use so many combos in hiv?

bc it replicates quickly and so develops resistance quickly

what are the purines

adenine and guanine

what are the pyrimidines?

cytosine, thymine, uracil (in ya rna 🙂 )

what are some NRTIs that are nucleosides (no phos)

Abacavir

Zidovudine

Lamivudine

Emtricitabine

what are some NRTIs that are nucleotides (YES phos)? why important?

Tenofovir

• needs fewer activation steps than SIDES

where do NRTIs have to be activated from prodrug

must have 5- phosphorylation (shown in green)

what do NRTIs lack so that DNA cannot keep getting made

3-hydroxyl group (shown in yellow)

how are NRTIs normally administered? which does not have good bioavail

PO!

• good bioavailability

  • NOT tenofovir, the TIDE one (has phosphates)

so tenofovir is a prodrug— clipped before phosphorylated. what besides the disproxoil could be the produrg? what is perk?

alafenamide

• stable in plasma— gets activated INSIDE cells

what are some combo drugs that include tenofovir

biktarvy, Descovy, Genvoya, Odefsey, Symtuza

how NNRTIs dif than NRTIs

• NRTIs = fake nucleotides that get incorporated into viral DNA.

• NNRTIs = allosteric inhibitors that bind reverse transcriptase and bend it out of shape.

what are some NNRTIs

Efavirenz

Etravirine

Rilpivirine

Doravirine

allosterically binds reverse transcriptase to prevent binding

which class of drug as monotherapy develops rapid resistance

nnrti’s

what disease is nnrti’s specific to

HIV-1!!

what is advantage of second gen nnrtis?

Because of flexibility 2nd gen bind to both native as well

as drug-resistant mutant HIV-1

what does diarylpyrimidine nnrti mean

means second gen— more confirmational flexibility over first gen

what do INSTIs do

hiv integrase inserts the viral genome into the DNA of the host cell

INSTIs what stand for

Integrase Strand Transfer Inhibitors

• stop insertion into host genome so infection cannot keep going

what are some instis

Raltegravir

Elvitegravir

Dolutegravir

Bictegravir

Cabotegravir

important med chem term that means ketone and b-carbonyl kee to be just so to bind to metals in viral enzyme?

coplanarity

why no take di or trival cations with instis

literally drug is engineered to chelate metals in viral enzyme active site

how protease inhib for hiv work

prevents enzyme HIV protease from budding from cell wall

how the HIV protease inhibitors owrk for med chem level

the hydroxyl-bearing sp3 carbon looks like that lovely tetrahedral intermediate that normally forms in peptide cleavage that causes budding, but since not intermediate it is permanent bond

what drug must have aspartate residue

hiv protease inhibitors

what are some hiv protease inhibitors

think of the drugs that end in -navir:

Darunavir ⭐ (very high yield)

Atazanavir

Ritonavir

Lopinavir

Saquinavir

Indinavir

Nelfinavir

Fosamprenavir

Tipranavir

Oseltamivir brand

tamiflu

Zanamivir brand

relenza

baloxavir marboxil

xofluza

Acyclovir

zovirax

valacyclovir

valtrexf

famiciclovir

famvir

ganiciclovir

cytovene, zirgan

valganiciclovir

valcyte

Nirmatrelvir/ritonavir brand

paxlovid

remdesivir

veklury

Glecaprevir/pibrentasvir brand

Mavyret

sofosbuvir/velpatasvir brand

Epclusa

Lamivudine brand

epivir

Emtricitabine/tenofovir disoproxil fumarate brand (nrti backbone)

truvada

emtricitabine/tenofovir alafenamide brand (nrti backbone)

descovy

Dolutegravir (insti)

tivicay

cabotegravir (insti)

Vocabria®, Apretude

Bictegravir/emtricitabine/tenofovir alafenamide (complete regimen) brand

Biktarvy

Dolutegravir/lamivudine (complete regimen) brand

dovato

Abacavir/dolutegravir/lamivudine (complete regimen) brand

triumeq

Dolutegravir/rilpivirine brand (complete regimen)

juluca

• think could be doctor, could be jd!

Cabotegravir/rilpivirine brand (complete)

cabenuva

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide brand (complete regimen)

Genvoya

elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (complete regimen) brand

Stribild