b group next week
1 messages over —, 2020-01-23 – 2020-01-23.
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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