B Group Next Week
Chairman Paul Letter to DNI Gabbard, pp.7-14 · letter_dni:email:00004
Page text: p.7, p.8, p.9, p.10, p.11, p.12, p.13, p.14 · original PDF
- Date
- 2020-01-23 14:07
- Type
- email · email
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Hi Ralph,
A spot has opened up on the agenda for Day 2 (Wed), and the Sponsor believes that the best replacement
might be any thoughts you might be able to provide on the current Coronavirus situation.
No slides are expected at this late date of course, as the Sponsor believes that just your insights would be
highly valuable. But if you have any artifacts handy we could certainly position them for you.
Please let me know at earliest convenience if you might be in a position to speak, and if so how much time you
might prefer.
2019-nHCoV
Baric Laboratory
University of North Carolina
Introduction
Outline
Emerging Coronaviruses
-- SARS-CoV, MERS-CoV
-- Pre-pandemic SARS-like Bat-CoV
-- 2019-HCoV
* Genome Organization and relatedness
The Outbreak
-- Origins
-- Disease
-- Human to Human Spread
Countermeasures
-- Broad based CoV nucleoside inhibitors
Summary
Group 2C
E
aici
Group 1B
Group 2D
B
SARS-like
Contemporary Human
Pre-epidemic
Coronaviruses
HCoV OC43
ete
HCoV HKU1
HCoV NL63
HCoV 229E
U
al = 2019-nHCoV
~~~ __ Bat strains 96% identical
Timeline: Emerging Nidovirus
Virus
Species
Emergen
HCoV-NL63
Human
HCoV-229E
Human
HCoV-OC43
Human
PEDV
Porcine
PRRSV
Porcine
BCoV
Bovine
SARS-CoV
Human
MERS-CoV
Human
SADS-CoV (HKU2) Porcine
2019-nHCoV
Human
500-800
200-300
~120 yea
~25 year
~25 year
~20 year
~16 year
~7 year
4 year
2 mont
Fu et al., 2018 Infect Genetic Evolution; Peiris JS et al., Lancet 2003, Huynh J
Zaki
AM et al.,
N Engl J Med. 2013, Mole B. Nature. 2013; Zhou P et al., Nature
Drivers of CoV Evolution
@ CoV Genome Size: 32Kb
__, CoV Replicas
@ CoV Mutation Rate
I ea
a 10°
--> Regulated Fidelity g
(nsp14: ExoN)
u Environmental Change
@ Fidelity rates change
Cnn
é
:
.
ee
e High Rates RNA Recombination
=< ~
m 25% during mixed infections
Repleatve re
mw Modular evolution
cS)Bc
Position Piece: CoV: An RNA Proofreading Machine Regulates Replication and Fidelity (RNA Biol. 2011), Du
Eckerle et al., Plos Pathogens 2010; Graham et al., Nature Medicine 2012; Smith et al., Plos Path 2014
Drivers of CoV Evolution
e CoV Genome Size: 32Kb
esa Remneae
e CoV Mutation Rate
oi
a 10°
Regulated Fidelity { » /
--_--_---->>
}
(nsp14: ExoN)
\
/
» Environmental Change
Fidelity rates change
Ga,
:
a
nea
e High Rates RNA Recombination
G7
m 25% during mixed infections
= Modular evolution
@ Plastic Surface Glycoprotein