Module #5 - Antivirals Flashcards
class 1 pathogens + example
no risk/limited risk
can work on an open lab bench in p1 protection
ex. e coli
class 2 pathogens + example
moderate risk
somewhat limited access to lab
special laminar fume foods used for protection against airborne versions of virus
p2 protection
ex. herpes virus
class 3 pathogens + example
risk of death or serious illness
could be low death rate, but high infection rate
restricted access to lab (special training/certification required)
special equipment required
all liquids/air coming in/out is filtered/treated
everything coming out is autoclaved + incinerated
ex. HIV (aids), Y. pestis (plague), covid
class 4 pathogens and example
incredibly infections and dangerous
lab accessed by airlock
special training required
space suit worn, shower going in/out
low pressure in lab
everything filtered/incinerated going in and out
ex. ebola, Marburg, lassa fever, hanta virus, smallpox
general structure of a virus
consists of genetic information (DNA or RNA - double or single stranded ) surrounded by a capsid
some viruses carry additional proteins in capsid such as virus proteins or enzymes
what is a capsid made of?
proteins
describe viruses that are enveloped
capsid surrounded by a membrane that is essentially a remnant of a host cell membrane
contains viral proteins
what is common to all viruses
all duplicate genetic information
produce viral protein
typically also interact with host proteins in some way and interfere with the way it operates
what is cytomegalovirus
causes respirator diseases in young children
what is papillomavirus
causes warts and cervical cancer (CC is an infectious disease caused by virus)
what are difficulties involved with developing antivirals
viruses are all unique (so one antiviral can’t be used for multiple viruses)
most viral proteins act by binding to a host protein
-these 2 proteins binding together creates a huge molecule (so hard for small molecule drug to break apart)
viruses have similar symptoms (so difficult to diagnose)
viruses constantly evolving (resistance)
most viral enzymes used to make nucleic acids (and having same substrates as host enzymes makes it hard to selective inhibition)
what is the best target for an antiviral
a viral enzyme, ideally not involved in nucleic acid replication
do viruses have a lot of enzymes?
no only 1-2 usually (which makes it hard to find good targets)
why are viral enzymes good target
because enzymes typically operate on small molecules
therefore a smaller drug can be used
why is using a viral enzyme as a drug target difficult
because viruses have very few enzymes (typically use protein protein association instead)
AND most viruses that have enzymes are involved in genetic replication - which is hard because we also have enzymes in body that replicate genetic info
-the shape of viral enzyme is similar to human enzyme (so it is hard to block viral without killing host enzyme)
ISSUE = how to kill virus without killing person
what are three viruses that actually have good antiviral drugs (and what do antiviral drugs aim to do)
hepatitis C (cure)
herpes (treat)
HIV (manage)
what are the three main issues with antiviral drugs
selectivity = killing virus without killing host (due to enzyme target issues)
diagnosis = viruses produce similar symptoms + drugs are made specifically for single viruses
resistance = very high mutation rates + resistance
what has been the greatest achievement for viruses
immunization
life cycle of virus
virus gets into a cell by sticking to a molecule on the outside of the cell (through nonbonding interactions), then penetrates/absorbs into it
capsid opens and releases genetic info
synthesis of regulatory proteins, RNA/DNA, and structural proteins (virus changes how host cell operates - get it to start doing viral stuff instead of cellular)
assembly of viral particles
viral particles get released from host cell
what is involved in absorption/penetration step of viral lifecycle
virus binds to protein on outside of host cell + capsid binds directly
if enveloped, envelope fuses with host cell membrane
capsid released into cell
is the absorption/penetration state a good drug target?
no because binding involved protein-protein interactions (very large therefore large drug required)
what occurs with releasing of viral nucleic acid into cell? is this a good target for drugs?
involve uncoating of viral nucleic acid
capsid opens and releases genetic info into the cell and into the cytoplasm
bad target because involved protein protein interactions
ph changes also occur which makes it difficult for drugs to interfere
what happens in the synthesis of regulatory proteins phase? is it a good target for drugs
viral proteins are made and take over normal cell systems
-nucleic acid replication
-expression of viral protein
-suppression of host cell defences (apoptosis)
-binding to host proteins
not good target: involves protein protein interactions
what happens in synthesis of RNA/DNA stage? is this a good target for dugs?
viral genome replicated using RNA/DNA depending on virus structure
enzyme required for this - therefore this is a good target for drugs because there is an enzyme available and the drug can prevent viral nucleic acid synthesis
what occurs in the synthesis of structural proteins stage of virus life cycle? is this a good target for drugs?
viral genes used to make viral proteins utilizing the host ribosome to alter the function of the cell
bad target for drugs because ribosome is involved
what happens in assembly stage of virus life cycle?
capsid proteins self assemble (has nucleic acid on inside and viral proteins on the outside) around viral DNA or viral RNA
unlikely to target drugs (unless viral enzymes are used)
what happens in release stage of virus life cycle? can be used as drug target?
release from cell: and be budding (cell remains intact and acts as little virus factory) or lytic (is destroyed)
unlikely target unless viral enzymes are used
what is the main requirement to use a viral enzyme as drug target? why is this tricky
there has to be a viral enzyme to take advantage of that is structurally unrelated to host human cells
important so that drug will target virus - not the human
trick because most viral enzymes involved in nucleic acid replication (which human cells also involved in)
describe general characteristics of herpes
causes chronic recurrent infections
can escape immune system destruction by hiding in nerve cells
every so often virus is activated, and outbreak occurs in body
what are the two types of herpes
HSV-1 (common) and HSV-2 (STD version)
symptoms of HSV 1
cold sores on mouth, nose and eye
80% of population infected, but only 10-20% get outbreaks
virus hides in nerve cells, but things may happen to activate (stress, sunlight)
what causes outbreak of HSV 1
triggers like sunlight, stress, or immune suppression
virus travels down axons of nerve cells to epithelial cells causing outbreak
what type of infection is HSV 1 + characteristics
lytic infection
viral activity is short (less than 24 hours), but experience lasts for a week because of overreaction of immune system
drug must be therefore administered quickly
what is hsv-2
STD version
sores on anus and genitals
15-20% of population
short viral activity - immune system overreacts
drug must be administered quickly
structure of herpes virus
genetic information is double stranded DNA
lots of genes (more than 70)
has its own polymerase - an enzyme used to make nucleic acid
what is the drug target of herpes
its own polymerase
what are the components of nucleic acid
nucleosides (what nucleotides are composed of)
sugars linked to base (2-deoxyribose in DNA or ribose in RNA)
base (heterocycle - ring with atoms that aren’t carbons)
describe the alphabet of bases
four different bases (ATCG) that are recognized by other molecule due to shape/H bonding pattern
each base recognized as different part of alphabet
describe the structure of nucleic acids
nucleosides are connected together through phosphate esters to form nucleotides
essentially is a backbone of sugars and phosphates with one base per sugar
where is informations stores in nucleic acid strands
in the sequence of bases
describe types of strands in DNA/RNA and what the function of number of strands is
both DNA and RNA can be double or single stranded
structure of double stranded nucleic acids
the bases on one strand must match up to their corresponding complementary base on the opposite strand in order for two strand to stick together
purpose of double stranded nucleic acids
stabilizes the molecules
error checking
second strand provides easy way to replicate/read information
what is the purpose of polymerases
is the