C.p.p

Question 1

CoViD Virus genome

Answer 1

29,811 RNA bases

25-29 proteins

Question 2

Center for structure Genomics of Infectious Diseases (CSGID) consortium

Answer 2

A consortium of 8 institutions set up to rapidly investigate the structures of emerging infectious agents.

Has solved 12 unique SARS-CoV-2 proteins

Question 3

Gene construct

Answer 3

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)

Question 4

Used to visualize structure of protein

Answer 4

X-ray Crystallography or Cryo-electron microscopy (cryo-EM). Both take months or years

Question 5

X-ray crystallography

Answer 5

Involves growing tiny crystals of pure protein and revealing their internal structure by bombarding them with x-rays from a high-energy electron beam.

Question 6

Cryo-electron microscopy (cryo-EM)

Answer 6

Scanning flash frozen proteins using a high-powered electron microscope.

Question 7

70-80% of covid sequence is similar to SARS-CoV

Answer 7

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

Question 8

M*pro

Answer 8

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

Question 9

HKU1

Answer 9

Cause for common colds similar to SARS

Question 10

MER’s virus

Answer 10

Similar to SARs virus also cause cold symptoms like HKU1

Question 11

Protein data bank (PDB)

Answer 11

Open-access digital resource for 3D structures of biological molecules

Question 12

M*pro crystal structure

Answer 12

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

Question 13

Spikes protein

Answer 13

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

Question 14

Berlin lab m*pro structure

Answer 14

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

Question 15

13a

Answer 15

A small-molecule inhibitor docked to M*pro active site, (it was designed to inhibits the MERs virus)

Question 16

13b

Answer 16

An altered version of 13b

safe and accumulates well in the lungs (Rox)

Question 17

SARS-CoV-2

Answer 17

Coronavirus spike protein has small molecular differences in it’s binding region compared with that of SARS-CoV

Question 18

Diamond structures

Answer 18

Spike protein, M*pro, second protease and replication machinery complex.

Have also identified 91 chemical fragments that bind to M*pro

Question 19

Ebselen

Answer 19

Drug that can disable M*pro

Question 20

RNA-dependent RNA polymerase (RdRp)

Answer 20

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

Question 21

COVID Moonshot

Answer 21

Non-profit crowd sourced initiative. Put up to persue chemists to use the 91 (and counting) fragments to design antiviral drug candidates

Question 22

Compound 77

Answer 22

Compound that inhibits SARS-CoV has been shown to also have antiviral activity against SARS-CoV-2

Question 23

ORF8

Answer 23

Protein in Covid virus who’s function is not understood yet

Question 24

nsp3

Answer 24

A large protein that the viruses use to shut down host-cell defences.

Question 25

Remdesivir

Answer 25

Binds to the active site of RdRp