Lecture 10 2/13/24 Flashcards
Why do very few antiviral drugs exist?
-compounds interfering with virus growth can adversely affect the host cell
-some medically important viruses cannot be propagated, have no animal model, and are dangerous (ease of handling)
-need to completely block virus replication, not just partially (otherwise leads to resistance)
-acute infections are short in duration
Why is drug resistance common in viruses?
-viruses replicate efficiently
-modest to high mutation frequencies
What are the dangers of drug resistance?
-patient cannot be treated with same drug
-infection can be unstoppable if other drugs do not exist
What is the main mechanism of drug resistance in RNA viruses?
error prone RNA polymerase, which typically has no correction mechanism
Which RNA viruses do encode for a proofreading exonuclease?
nidoviruses
Why do DNA viruses evolve more slowly and with less diversity compared to RNA viruses?
DNA polymerases can excise and replace misincorporated nucleotides
What are the characteristics of monoclonal antibodies?
-uses immunoglobulins from previously infected individuals as a drug
-provide temporary protection against a virus
What are entry inhibitors?
drugs that prevent viruses from entering and infecting host cells
What are the characteristics of Symmetrel/Amantadine?
-interacts with influenza viral M2 protein
-blocks entry of protons into virion, preventing uncoating
What are the characteristics of Maraviroc CCR5 inhibitor?
-blocks CCR5 receptor
-prevents HIV/AIDS virus from entering and infecting host cells
What are polymerase inhibitors?
drugs that target the viral replication process by inhibiting viral polymerase activity
What are nucleoside inhibitors?
a type of polymerase inhibitor that gets incorporated into the viral genome, causing premature termination of the replication process
What are non-nucleoside inhibitors?
a type of polymerase inhibitor that binds to the viral polymerase and inhibits its activity
Which type of polymerase inhibitor is Acyclovir?
nucleoside inhibitor
What is important about the ester derivative version of Acyclovir?
-releases Acyclovir when the ester is cleaved by cellular enzymes
-markedly improved bioavailability
What are the characteristics of Remdesivir?
-inhibits replication of RNA viruses through mutagenesis
-must be delivered intravenously
What are the characteristics of integrase inhibitors?
-treat HIV/AIDS
-prevent viral integrase enzyme from inserting viral DNA into host genome
What are the characteristics of endonuclease inhibitors?
-inhibit influenza endonuclease
-prevents the endonuclease activity required for transcription and replication
What are the characteristics of protease inhibitors?
-block protease enzymes from processing the viral proteins
-interfere with viral replication and maturation
What are the characteristics of neuraminidase inhibitors?
-target influenza
-prevent release of new viruses from the cell
-mimic the natural sialic acid ligand
What are the characteristics of RdRp nucleoside analog?
-broad spectrum
-believed to cause mutations in virus genome
-decreases ability of virus to replicate
Why is combination therapy important?
-drugs suppress replication
-using multiple drugs at once allows for suppression of viruses that otherwise would have developed mutations to one of the drugs