Antivirals Flashcards
What are viruses?
Obligate intracellular parasites (rely on a host cell to reproduce)
How do viruses exist outside on infected cell?
Virions
How many proteins can viruses encode?
~4
What do virions consist of? (3)
dsDNA or ssDNA, lipid envelope (from host cell) and protein coat/capsid (both can contain antigenic glycoproteins
How big are virions approx?
1/100 of a bacterium
What is the viral range?
Group of cell types/species that virus can infect
What is a virus that only infects bacteria?
Bacteriophage
What are viruses that infect plants and animals?
Plant viruses and animal viruses
Can animal viruses infect other (cross) phyla?
No, but may affect closely related species
How are viruses classified? Diff categories?
Shape of capsid; helical, icosahedral, complex
What is pathogenicity?
Ability of viruses to cause disease (not all cause disease)
What is virulence?
Degree of pathogenicity (intensity of disease)
What is virus latency?
Ability to remain dormant in an organism
What is the virus that causes chicken pox and shingles?
Varicella zoster
How does chicken pox exhibit latency?
Can remain dormant in body and remerge later in life as shingles
What are people chronically infected and serve as reservoirs of infectious virus?
Carrriers
What are 4 stages of virus life cycle?
Absorption, penetration, replication, release
What determines virus range and initiation of infection process?
Proteins on surface of virus (antigen) that bind to protein receptors in host cell
What occurs once virus has access to host cytoplasm?
Viral DNA or RNA crosses pmemb to to cytoplasm or nucleus
What occurs to viral DNA or RNA once inside host cell?
Interacts w/ host machinery to translate DNA/RNA into viral proteins
What is the 4th stage of a viral life cycle (release)?
Newly synthesized virion particles are release to continue infection cycle
What are the 2 types of viruses?
RNA or DNA viruses, can be double stranded or single stranded
How does a DNA virus transcribe and translate its specific proteins in a host?
Viral DNA incorporates genome w/ host’s (in nucleus) and is transcribed into mRNA w/ host DNA-dependent RNA polymerase, mRNA in translated into viral proteins
Are DNA viruses usually ds or ss?
Double stranded
What are poxviruses able to do?
Can replicate in hosts cytoplasm as they carry their own DNA-dependent RNA pol (are a DNA virus)
What is required for viral genome REPLICATION?
DNA-dependent DNA pol (from host)
How does a RNA virus transcribe and translate its specific proteins in a host?
Require an RNA-depended RNA pol (RNA -> mRNA)
What are the 2 purposes of RNA-dependant RNA pol?
Transcriptase (transcribe mRNA) and replicase (replication)
Where do most RNA viruses complete their replication? Exception?
Host cell cytoplasm; influenza in nucleus
What are retroviruses?
Viruses that have RNA genome (ss) that directs DNA formation from RNA
What is reverse transcriptase?
Viral enzyme that turns viral RNA into DNA
What is reverse transcriptase aka?
RNA-dependent DNA pol
What occurs to viral DNA from a retrovirus?
Is integrated w. Host DNA and transcribed in mRNA and translated into proteins (by host enzymes)
T/f: most retroviruses immediately kill their host cells
False, infected host cells can continue to replicate w/ proviral DNA
What is an ex of a retrovirus?
HIV
What is the best/cheapest/effective what to prevent viral infections?
Vaccinations
Approx. how many infections are their vaccines for?
13 (14 w/ COVID?)
What can vaccines contain? (4)
Live-attenuated (cant replicate) or killed viruses, viral proteins or mRNA (antigens)
How do vaccines work?
Cause host to generate antibodies for virus to decr response to 2nd infection
How do antiviral drugs work?
Exert actions at several stages of viral life cycle (treat after infection)
What are 5 targets of antiviral drugs?
Stages of viral life cycle: viral entry, nucleus acid synthesis, protein synthesis, viral packaging, and virion release
What can antiviral combination therapy allow for?
Incr clinical effectiveness and prevent/delay resistance
What does “anti-viral drugs are virustatic” mean?
Only work against replicating viruses (not latent/dormant)
What is acyclovir?
Anti-herpes drug that is a nucleoside analog (fake DNA building block) which viruses incorporate into genome during repl’n
How does acyclovir cause DNA chain termination?
Lacks an -OH group that is needed for chain elongation of the DNA backbone
What is the result of acyclovir causing chain termination?
The virus life cycle is halted since newly synthesized DNA is inactivated
Why does acyclovir only affect viral DNA if humans also rely on guanine (its NT analog)?
Herpes thymidine kinase has affinity 200x greater for acyclovir vs mammalian thymidine kinase (specificity)
What must occur to acyclovir before it can be incorporated into viral DNA?
Phosphorylated into acyclovir-triphosphate, herpes thymidine kinase adds first phosphate group (host has own thymidine kinase)
What 3 ways can herpes simplex virus have acyclovir resistance?
Impaired viral thymidine kinase production (decr acyclovir phos’n and DNA incorp.), altered thymidine kinase substrate specificity (phos’n of thymidine vs acyclovir), altered viral DNA pol (integrates normal NT vs acyclovir)
What is HIV?
Human immunodeficiency virus; a retrovirus (lentivirus) that causes chronic/persistent infection w/ gradual onset symptoms
Which cells and receptors does HIV infect?
T cells; CD4+
What occurs when CD4+ T cell levels decline below a critical level after HIV infection?
Host loses cell-mediated immunity and is susceptible to opportunistic infections (AIDS)
T/f: there is a period of viral latency after HIV infection
False, repl’n is constant after infection (wo/ treatment)
T/f: anti-viral HIV drugs only target one step of viral life cycle
False, drugs can target multiple levels (fusion, transcription, integration, viral release)
Currently, how many antiretroviral drugs are used to treat HIV?
Usually 3 or more together
What is highly active retroviral therapy (HAART)?
Drug combinations that can slow/reverse viral RNA production (HIV disease progression)
What occurs at the beginning of HIV infection?
Gp120 (HIV envelope proteins) bind to CD4 and CCR5 receptors on T cells
What are entry inhibitors for HIV?
Antivirals that interfere w/ binding, fusion, and entry of HIV virion into human call
What is maraviroc?
CCR5 receptor antagonist that interferes w/ HIV binding to T cell
What is reverse transcriptase?
HIV enzyme that converts viral RNA into DNA using host nucleosides (RNA dependent RNA pol)
What are nucleoside reverse transcriptase inhibitors (NRTIs)?
Small molecule drugs that resemble host nucleosides and are incorporated into new HIV DNA (by reverse transcriptase)
How do NRTIs cause chain termination?
NTRIs lack 3’-OH on ribose ring (prevent elongation)
What provides NTRIs w/ viral specificity? (Ie. don’t affect mammalian transcription)
Mammalian RNA (DNA to RNA) and DNA pols (DNA to DNA) are distinct enough from viral reverse transcriptase (RNA to DNA)
What is integrase?
Viral enzyme that inserts viral/HIV DNA into host genome
What are integrase strand transfer inhibitors (INSTs)?
Block activation of integrase and inhibit viral DNA incorporation into host genome (inhibits HIV proliferation)
What is an ex of a INST?
Raltegravir
What are aspartase proteases?
Viral enzymes that are required for assembly of HIV virions (cleave precursor proteins for mature virion core)
What are HIV protease inhibitors?
Antivirals that bind to and inhibit aspartase proteases (active site ligand analog) that prevents new HIV from becoming mature
T/f: HIV protease inhibitors are usually used w/ reverse transcriptase inhibitors
True
What is amantadine?
Anti-influenza drug that inhibits uncoating of influenza A virus (early step in replication)
What is the M2 protein?
Proton pump that permits acidification of virus core to allow activation of viral RNA transcriptase (onset of infection)
How does amantidine affect M2?
Blocks proton transfer through M2, blocking acidification and viral transcription
T/f: amantidine is prophylactive against influenza A not B
True
T/f: amantidine and block infection or reduce symptoms of influenza if given w/ 48 hours after contact
True
What is a resistant influenza A virus mutant?
H3N2
What is a more cost-effective strategy against influenza?
Vaccination
What is a possible treatment against influenza in high-risk/immunocompromised patients?
Seasonal prophylaxis using anti-viral drugs (if vaccine cant be administered)
What is zanamivir?
Anti-influenza drug that inhibits neuroaminidases produced by influenza A and B
What are neuroaminidases?
Enzymes that cleave sialic acid residues from viral proteins that enable virus to be released from host cell
How do neuroaminidase inhibitors (zanamivir) provide anti-influenza action?
Prevent viral spread (prevent release from host cell by neuroaminidases)