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1. WO2021243149 - PROTEIN COVARIANCE NETWORKS REVEAL INTERACTIONS IMPORTANT TO THE EMERGENCE OF SARS CORONAVIRUSES AS HUMAN PATHOGENS

Publication Number WO/2021/243149
Publication Date 02.12.2021
International Application No. PCT/US2021/034753
International Filing Date 28.05.2021
IPC
C07K 14/165 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
005from viruses
08RNA viruses
165Coronaviridae, e.g. avian infectious bronchitis virus
C12N 15/50 2006.1
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09Recombinant DNA-technology
11DNA or RNA fragments; Modified forms thereof
31Genes encoding microbial proteins, e.g. enterotoxins
33Genes encoding viral proteins
40Proteins from RNA viruses, e.g. flaviviruses
50Coronaviridae, e.g. infectious bronchitis virus, transmissible gastroenteritis virus
C12N 7/01 2006.1
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
7Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
01Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
CPC
A61K 39/12
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
39Medicinal preparations containing antigens or antibodies
12Viral antigens
C07K 14/005
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
14Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
005from viruses
C07K 2319/00
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
C07K 2319/50
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
KPEPTIDES
2319Fusion polypeptide
50containing protease site
C12N 2770/20022
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2770ssRNA Viruses positive-sense
00011ssRNA Viruses positive-sense
20011Coronaviridae
20022New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
C12N 2770/20034
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
2770ssRNA Viruses positive-sense
00011ssRNA Viruses positive-sense
20011Coronaviridae
20034Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Applicants
  • PRESIDENT AND FELLOWS OF HARVARD COLLEGE [US]/[US]
  • MEKALANOS, John, J. [US]/[US]
  • ROBINS, William, P. [US]/[US]
Inventors
  • MEKALANOS, John, J.
  • ROBINS, William, P.
Agents
  • BRAICH, Ravinderjit
  • RESNICK, David, S.
  • EISENSTEIN, Ronald, I.
  • FITZGERALD, Mark, J.
  • BENN, Susanna, C.
  • CROSBY, David, F.
  • HUFF, Shayne, Y.
  • PTASHKA, Teresa, A.
  • KLING, Nicole, D.
Priority Data
63/031,30628.05.2020US
63/032,92501.06.2020US
63/129,02922.12.2020US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) PROTEIN COVARIANCE NETWORKS REVEAL INTERACTIONS IMPORTANT TO THE EMERGENCE OF SARS CORONAVIRUSES AS HUMAN PATHOGENS
(FR) RÉSEAUX DE COVARIANCE DE PROTÉINES RÉVÉLANT DES INTERACTIONS IMPORTANTES POUR L'ÉMERGENCE DE CORONAVIRUS SARS EN TANT QUE PATHOGÈNES HUMAINS
Abstract
(EN) The methods and compositions provided herein, relate in part, to the discovery of conserved interactions between amino acid residues in all proteins encoded by SARS-CoV-related viruses. Accordingly, pairs and networks of residue variants that exhibited statistically high frequencies of covariance with each other can be used as a new computational approach (Covariance-based Phylogeny Analysis) for understanding viral evolution and adaptation. Provided herein is evidence that the evolutionary processes that converted a bat virus into a human pathogen occurred through recombination with other viruses in combination with new adaptive mutations important for entry into human cells.
(FR) Les méthodes et les compositions selon l'invention concernent, en partie, la découverte d'interactions conservées entre des résidus d'acides aminés dans toutes les protéines codées par des virus associés au SARS-CoV. Ainsi, des paires et des réseaux de variants de résidus qui ont présenté des fréquences statistiquement élevées de covariance les uns avec les autres peuvent être utilisés en tant que nouvelle approche computationnelle (analyse phylogénétique basée sur la covariance) pour comprendre l'évolution et l'adaptation virales. La présente invention démontre que les processus évolutifs qui ont converti un virus de chauve-souris en un pathogène humain se sont produits par recombinaison avec d'autres virus en combinaison avec de nouvelles mutations adaptatives importantes pour l'entrée dans des cellules humaines.
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