C.p.p Flashcards
Learn the contents of the article (25 cards)
CoViD Virus genome
29,811 RNA bases
25-29 proteins
Center for structure Genomics of Infectious Diseases (CSGID) consortium
A consortium of 8 institutions set up to rapidly investigate the structures of emerging infectious agents.
Has solved 12 unique SARS-CoV-2 proteins
Gene construct
A circle of DNA containing instructions for the protein. Contains regulatory sequences to decide where and how it is expressed.
How it’s used to create protein (‘structure’)
1) insert construct into living cells (e.coli)
2) purify protein after it is created by e.coli
3) image w/ crystallography or cryo-electron microscopy (cryo-EM)
Used to visualize structure of protein
X-ray Crystallography or Cryo-electron microscopy (cryo-EM). Both take months or years
X-ray crystallography
Involves growing tiny crystals of pure protein and revealing their internal structure by bombarding them with x-rays from a high-energy electron beam.
Cryo-electron microscopy (cryo-EM)
Scanning flash frozen proteins using a high-powered electron microscope.
70-80% of covid sequence is similar to SARS-CoV
With information of gene constructs, the new viral protein can be designed and predictions about existing inhibitors that might block the proteins can be made
M*pro
Covid main protease
Enzyme that cuts out (functional)
proteins from a long strand that the virus produces when it invades cells.
(Ribosomes of host cells produce the the long protein chain from the injected RNA sequence by the virus)
Made of two identical subunits and looks likes a motheaten heart, with an active enzymes site on each side of the structure
Has two active sites
HKU1
Cause for common colds similar to SARS
MER’s virus
Similar to SARs virus also cause cold symptoms like HKU1
Protein data bank (PDB)
Open-access digital resource for 3D structures of biological molecules
M*pro crystal structure
Found (made by shanghai team) with an inhibitor attached to it.
UK team focused on crystallizing the protein with no molecule attached, to identify active sites to which potential drug compounds might bind
Spikes protein
locks on covid, to human cells
Has crucial role in infection
The spikes on the virus attach to the ACE2 receptor found on lung cells and other parts of the body
Spike formed of 3 identical molecules stuck together in the shape of a pyramid
Binds ten times more tightly to ACE2 than to SARS-CoV
Berlin lab m*pro structure
Focused on the unbound Mpro structure and small docked molecule inhibitor called 13a. Made 13b and also found the structure of the Mpro bound to the inhibitor
13a
A small-molecule inhibitor docked to M*pro active site, (it was designed to inhibits the MERs virus)
13b
An altered version of 13b
safe and accumulates well in the lungs (Rox)
SARS-CoV-2
Coronavirus spike protein has small molecular differences in it’s binding region compared with that of SARS-CoV
Diamond structures
Spike protein, M*pro, second protease and replication machinery complex.
Have also identified 91 chemical fragments that bind to M*pro
Ebselen
Drug that can disable M*pro
RNA-dependent RNA polymerase (RdRp)
RdRp or nsp12 that forms a complex with nsp7 and nsp8
The enzyme that makes copies of the full viral genome (remdesivir binds to it’s active site)
A complex made of non-structural (covid) viral proteins that are in charge of replication and transcription
Produces viral RNA and RNA that is translated into new virus proteins by the host
In charge of the virus replication within the host
COVID Moonshot
Non-profit crowd sourced initiative. Put up to persue chemists to use the 91 (and counting) fragments to design antiviral drug candidates
Compound 77
Compound that inhibits SARS-CoV has been shown to also have antiviral activity against SARS-CoV-2
ORF8
Protein in Covid virus who’s function is not understood yet
nsp3
A large protein that the viruses use to shut down host-cell defences.
