MGY378 22,23: Antivirals

viral coat pr PRR

TLR2, TLR4

ssRNA PRR

TLR7, TLR8

hypomethylated CpG DNA PRR

TLR9

DNA PRR

cGAS

5’ triphosphate dsRNA PRR

RIG-I

dsRNA PRRs

MDA5, TLR3

Interferon

HBV, HCV

imiquimod

• HPV warts

• general activator

miraviroc

• HIV-1

• competes w gp120 for binding to CCR5

T20

• HIV-1

• peptide mimic

• prevents 6 bundle formation of gp41 needed for fusion

chloroquine/ hydroxychloroquine

• Influenza

• absorbs H+ to stop endosome pH decr

amantidine/ rimamantadine

• influenza

• blocks ion flow into M2

acyclovir (-ovir EXCEPT tenofovir)

• Herpes

• chain terminator

• lacks sugar moiety

• only in cells w viral TK

• Targets polymerase

foscarnet

• Herpes

• Blocks PPi binding site in virus polymerase ⊣ cleavage of PPi from dNTPs

remdesivir

• sars2

• Replaces ATP with RTP → elongation barrier → stalling of RdRp

• Induces chain termination 3 nt after its incorporation

molnupiravir

favipiravir

• sars2

• hypermutation (mistaken for C/U)

ribavarin

• broad spectrum

• GTP mimic - competitively inhibits inosine monophosphate dehydrogenase (IMPDH) → may reduce GTP pools ⊣ viral pol

lenacapavir

• HIV-1

• binds directly to capsid

• Entry: occupies same site as nuclear import factors > prevents import of capsid into nucleus

• Exit: interferes with capsid-capsid interactions of Gag

zanamivir (inhale)

oseltamivir (oral)

• influenza

• Mimics sialic acid

  • Viral NA cleaves terminal sialic acid to block SA:HA interactions → causes virus to not reinfect the same cell ⊣ viral release

HIV-1 protease inhibitor

• Bind catalytic site of protease and block interaction with viral proteins

• So all u gen are immature particles that come from the cell bcz they don’t have any of the enzymes required

Paxlovid (nirmatrelvir + rotanavir)

• sars2

• Prevents processing of viral polyprotein precursors orf1a, orf1ab which make the replicase

AZT

• HIV-1, HBV

• Missing the 3’OH on ribose sugar (for addition of next base)

• Chain terminator

tenofovir

• HIV-1, HBV

• Mimics dNTP

• Lacks the ribose moiety (like acyclovir, but this is for HIV and it targets RT)

• Chain terminator

Nevirapine

delavirdine

efavirenz

etravirine

• HIV-1 (only) NNRTI

• allosteric inhibition of RT → stuck RT

dolutegravir

• HIV-1

• Interfere with integrase > cut short the life cycle

• Long plasma half-life

  • Dissociation is 8X slower than RAL, 26X slower than EVG

  • High barrier to resistance

cabotegravir

• HIV-1

• Interfere with integrase > cut short the life cycle 

• Potency is lower than dolutegravir and BIC

• Long half-life (40 days) 

• Formulated as a nanoparticle injection 

• Given at prolonged intervals (once every 2 months) – convenient

cyclosporin A

• broad spectrum, HIV, HCV

• Inhibitor of cyclophilin A (proline cis-trans isomerase) ⊣ protein folding 

  • Splices cyclophilin A off 
    

• Hep C - cyclophilin A part of replication complex

• HIV - Cyclophilin A binds to capsid > stabilizes and allows capsid nuclear import

castanospermine

• flaviviridae

• Drug inhibits ER α-glucosidase I

  • Inhibition removes terminal glucose residue on N-linked glycans → disrupts viral pr folding

digoxin

• broad spectrum

• inhibit Na⁺/K⁺ ATPase (NKA) in PM → accum of Ca²⁺

• inhibits replication. 

• Alters RNA processing