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Susan Weiss Slides Susan R. Weiss Department of Microbiology Penn Center for Research on Coronaviruses and Other Emerging Pathogens Perelman School of Medicine University of Pennsylvania Coronavirus virion Spike (S) Nucleocapsid (N) entry: binding & fusion CAP tropism immune Membrane (M) response virulence Small membrane Protein (E) AA AA single‐stranded, Coronaviruses are a family within the Nidovirus non‐segmented, order; named for the nested subgenomic mRNAs positive sense RNA Hemagglutinin‐esterase (HE) genome generated during infection Coronavirus Timeline Bat SARS‐CoV CoVs OC43 Basic CoV Biology MERS‐CoV SARS‐CoV‐2 229E HKU1 Common cold NL63 OC43 can infect HKU1; Pneumonia lower respiratory NL63; Bronchiolitis, croup tract 1960‐70 1980 1990 2000 2010 2020 MHV model Animal viruses, vaccines Pathogenic human coronaviruses Human cold CoVs SARS‐CoV, MERS‐CoV, SARS‐CoV‐2 Severe acute respiratory disease coronavirus disease‐2019 or COVID‐19 SARS‐CoV interspecies transmission Human Horseshoe bat Civet Human to human close contact How many times did this happen? Over in eight months, 8098 infections, 9.6% mortality 87% in China and Hong Kong Images from various internet sites MERS‐CoV interspecies transmission limited human Human to human spread Neoromicia capensis Camel Bat Mostly in Arabian peninsula Camels are a reservoir for MERS‐CoV Still new cases 2020 2428 cases, 35% mortality Korea SARS‐CoV‐2 interspecies transmission ???? Intermediate species Bat Malayan pangolin Human Human to human spread 34.7 M infections 1,030,880 deaths US (10.02.20) 7.3 infections 209,318 deaths Coronavirus genome structure Conserved replicase proteins 16 nsps Accessory proteins Alphacoronaviruses 1a 1b 4a 5’ PLP1 PLP2 3CLpro 4b Duvinacovirus Pol Hel AAA3’ 229E, NL63 Setracovirus SPIKE EM N Betacoronaviruses 1a 5a 1b 2a 4 Lineage a, 5’ AAA3’ OC43, HKU1, MHV Embecovirus HE SPIKE EM IN 7a/7b8a/8b Lineage b, 1a 3a/3b 6 1b 5 9b Sarbecovirus 5’ AAA3’ SARS‐CoV SPIKE E SARS‐CoV‐2 M N 1a 4a 5 Lineage c, 1b 5’ Merbecovirus AAA3’ MERS‐CoV SPIKE 3 4b EM8b N Coronavirus conserved proteases and replicase ORF1a ORF 1b nsp 12 3 45678910 11 12 13 1415 16 nsp10 Papain‐like 3C‐like nsp8 activator nsp1 nsp16 protease(s) protease primase nsp13 nsp15 mulitple host RNA dependent mRNA processes helicase EndoU; antagonist polyprotein RNA polymerase dsRNA capping activities main protease RdRp NTPase nsp3 accumulation processes Replication of genome host antagonist polyprotein and transcription of activities nsp14 mRNAs DUB ExoN macrodomain remdesivir Proof reading mRNA capping How do we know SARS‐CoV‐2 was not engineered by humans? • Similar viruses are found in bats • It does not resemble any known recombinant viruses • It seems impossible that anyone would know how to design a virus with the properties of SARS‐CoV‐2 For the future • Vaccine development • Develop antivirals for future outbreaks or spillovers • Spike protein RBD may differ while replicase proteins are conserved • Continue to identify and characterize Coronaviruses and other viruses from bats and other species • Support basic virology research.
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