Lecture 7
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what is the first anti bacterial
-penicilin 1929 -inhibits bacterial cell wall synthesis -broad spectrum G+ve, some G-ve
what was the first anti-viral
-iododeoxyuridine by william prussoff 1962 -inhibits viral nucleic acid synthesis -works well against topical herpes virus
how many people were infected with hcv before?
170 million peeps 268 000 canadians
hcv was responsible for how much of chronic liver disease
40-60% leading cause of liver transplant
what is the % of hcv infected people get chronically infected
85%
true or false: there is no vaccine for hcv
true
what is chronic hcv aka how much time does it take to call it chronic
continuing hcv related disease without improvement for at least 6 months
how many % of hcv peeps show no symptoms
60-80% slowly progressing lifelong disease
how many hcv peeps get cirrhosis and liver failure
10-20%
how many % of peeps get hepatocellular carcinoma due to hcv
3-5%
typically clinical symptoms appear during when for hcv peeps
during liver failure -20y may elapse between infection and development of serious complications
who got the med nobel prize in 2020
-harvey alter, michael houghton and charles rice -for discovery of hep c
true or false: chronic hcv is a curable disease
true
treatments of hcv from 1990 to 2001
-mostly inf started at like 5% response rate to 50% response rate
hcv treatment in 2011 and 2014
-inf+pi or NI 2011 -peg inf RBV -75% response rate 2014 -peg inf rbv pi (DAA) or NI -90% response rate
2015 hcv treatment
-inf free daas -o2/o3 (DAA) -close to 100% response rate
what does ns2 do in hcv
it autocleaves itself for other non structural viral replication
what are the 3 targets for hcv meds
-ns3 pro inhibitors -ns5a inhibitors -ns5b inhibitors
what is the ns3 protease
-trypsin like serine protease -his, asp, ser at the catalytic triad -pivotal role in polyprotein processing -screening of small molecule compound library=no specific hits
what do high throuput molecule screenings do
screen for possible molecules that work against pathogens usually uses multi well plates with robots
what is the catalytic site for ns5a/b
ddivpc
n terminal product inhibition is observed for ns3/4a what is the sequence and the KI
ddivpc -79um aka mid inhibition
what is cellular potency aka ec50
it is the minimum amount of the drug to kill 50% of the pathogen
what is ki
intrinsic potency