Lecture 6: Covid

Question 1

Overview

Answer 1

→ ACE2 receptor that binds RBD
→ + ssRNA
→ four genera: a, b, y, d
→ spike proteins

Question 2

Polyprotein

Answer 2

replicase polyprotein PP1ab
→ PL protease and main protease cleavage site

Question 3

Coronavirus vaccines

Answer 3

mRNA, vector, protein, inactivated virus

Question 4

4 Drug targets

Answer 4

Immunomodulators

Entry inhibitors

Protease Inhibitor

Transcription and RT Inhibitors

Question 5

Entry inhibitors
→ mechanism of entry
→ 2 drug

Answer 5

spike protein requires 2 proteolytic cleavages
→ S1/S2
→ receptor engagement
→ S2’
→ fusion peptide exposed
→ ionic changes for fusion peptide insertion
→ priming for membrane fusion>

Drug
→ APN01
→ competes with ACE2 for virus binding
→ reduces inflammatory responses

monoclonal antibodies
→ target spike protein
→ therapy early during infection

Question 6

Immune Modulators

2 drugs and mechanism

Answer 6

→ late phase → aggresive inflammatory response

→ IL-1 receptor blocker Anakinra
→ unspecific antiinflammatory response

→ JAK/STAT inhibitor Baricitinib
. → later step, but also unspecific

Question 7

Replication inhibitors

→ characteristics of replication
2 drugs and mechanism

Answer 7

RdRp inhibitors

proofreading function present

drugs
→ Remdesivir (broad spectrum)
→ only stalls RdRp after addition of 3 more nucleotides to circumvent proofreading activity
→ Molnupiravir (broad spectrum)
→ stable base pairs with G/A in catalytic center of RnRp to prevent proofreading function

Question 8

Protease inhibitors
→ 2 proteases
→ drug

Answer 8

TMPRSS2

Main protease
→ 3 domain
→ Chymotrypsin like proteases
→ cleaves polyprotein at 11 sites
→ Peptidomimetics inhibit protease
→ Paxlovid (Nirmetralvir & Ritonavir)
→ Ritonavir just slows down breakdown as
inhibitor of Cyt 450 to allow lower dose