Antivirals Flashcards
virus
obligate intracellular parasite: rely on host biosynthetic machinery to reproduce
exist as independent particles when not inside an infected host (virions)
encode ~4-200 proteins
virions
double or single stranded DNA or RNA
a protein coat (capsid)
some have a lipid envelope derived from the host cell - may contain antigenic glycoproteins
viral range
group of cell types or species a virus can infect
not a lot of cross-species viruses
viral shape
classified based on shape of capsid
- helical
- icosahedral
- complex
pathogenicity
ability of viruses to cause disease
degree of pathogenicity is virulence (how strong of an infection they cause)
varicella zoster
chicken pox is the primary V2V infection - presents with blisters
virus is dormant in host - V2V latency (in dorsal root ganglia)
reactivation of virus = shingles
chronically infected = carriers
viral replication cycle
absorption, penetration, replication, release
proteins on surface of virus bind to receptor protein on host cell → interaction determines the host range of virus + begins infection
viral DNA/RNA crosses plasma membrane to cytoplasm or nucleus → interacts with host machinery to translate the DNA/RNA into viral protein
newly synthesized virion particles are released to continue infection cycle
central dogma of biology
DNA → mRNA → protein
DNA can be transcribed into mRNA or replicated (in the nucleus)
protein translation (mRNA → protein) happens in the ribosomes - cytoplasm
DNA viruses
enter the host cell nucleus → viral DNA is integrated into host genome and transcribed into mRNA - host DNA-dependent RNA polymerase
mRNA is translated into viral proteins
further replication of viral genome requires DNA-dependent DNA polymerase
virus uses host machinery (exception: poxviruses - carry own and replicate in cytoplasm)
RNA viruses
double stranded - bring own machinery: RNA-dependent RNA polymerase → transcriptase and replicase
most replicate in cell cytoplasm
retroviruses
RNA genome directs formation of DNA molecule
RNA→DNA→mRNA→protein
viral enzyme - reverse transcriptase is RNA-dependent DNA polymerase → copies viral RNA into DNA
viral DNA is integrated into host DNA → host enzymes take over
vaccinations
cheap + effective way of preventing viral infections
consist of live-attenuated or killed viruses, or viral proteins or mRNA (antigens)
anti-virals
drugs that interfere with stages of viral replication → viral entry, nucleic acid synthesis, protein synthesis, viral packaging, virion release
combination therapy → greater clinical effectiveness + delay of resistance
virustatic: only active against replicating viruses and don’t affect latent virus (effect is on replication cycle)
acyclovir
anti-herpes drug
nucleoside analog = DNA chain termination → virus incorporates into genome during replication = halts life cycle
must be phosphorylated to acyclovir-triphosphate to be incorporated into viral DNA as a terminal substrate
enzyme specific to herpes simplex virus (thymidine kinase) adds first phosphate group
acyclovir resistance
can result from:
- impaired production of viral thymidine kinase
- altered thymidine kinase substrate specificity (e.g. phosphorylation of thymidine but not acyclovir)
- altered viral DNA polymerase
HIV
human immunodeficiency virus
lentivirus → retrovirus that leads to chronic persistent infection with gradual onset of clinical symptoms
HIV infects human immune cells (CD4+ T cells)
replication is constant following infection
AIDS
acquired immunodeficiency syndrome
CD4+ T cells decline below a critical level → cell mediated immunity is lost and body becomes susceptible to opportunistic infections
death is caused by infections that would normally be mediated by immune system
anti-viral HIV drugs
target viral infection at multiple levels: fusion, transcription, integration into host genome, virion release
usually combine 3+ antiretroviral drugs
highly active antiretroviral therapy (HAART) - drug combinations that can slow or reverse the increases in viral RNA load that normally accompany progression of disease
entry inhibitors
HIV infection begins with attachment of HIV envelope proteins called gp120 to CD4 and CCR5 receptors on surfaces of T cells → binding allows entry
entry inhibitors interfere with binding, fusion, and entry of HIV virion into human cell
Maraviroc
CCR5 receptor antagonist
interferes with HIV binding to T cell
entry inhibitor
reverse transcriptase
HIV enzyme that synthesized DNA from HIV RNA using nucleosides in the host T-cell
RNA dependent DNA polymerase
nucleoside reverse transcriptase inhibitors
small molecule drugs that are similar to the host cell nucleosides and are incorporated into new HIV DNA chain as if they were endogenous molecules
only incorporated by reverse transcriptase (does not affect mammalian polymerases)
lack a 3’hydroxyl group on ribose ring = impossible to attach next nucleoside → chain termination
integrase strand transfer inhibitors
integrase is a viral enzyme that inserts viral genome into the DNA of the host cell
integrase inhibitors block the action of integrase to inhibit HIV proliferation
ex. Raltegravir
aspartate proteases
enzyme that cleaves precursor proteins to form the final structural proteins of the mature virion core
critical in assembly of infectious HIV virions
