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Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome

Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome
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Germany
Switzerland
Swiss
National-center
Irish-research-council-advanced-laureate
Protein-data-bank
Swiss-national-science-foundation
Electron-microscopy-data-bank
Carbery-group-ltd
Ministry-of-education
Creative-commons-attribution

Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes

Most analyses of the antibody responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have focused on antibodies cloned from memory B cells. This approach has led researchers to conclude that neutralizing antibodies (nAbs) primarily target the receptor-binding domain (RBD) of the virus s spike protein. Voss et al. took a different approach, using proteomic deconvolution of the serum immunoglobulin G antibody repertoire from four COVID-19 convalescent patients. They found that the nAb response was largely directed against epitopes such as the N-terminal domain (NTD), which lie outside the RBD. Several of these nAbs were shared among donors and targeted an NTD epitope that is frequently mutated by variants of concern. Science , abg5268, this issue p. [1108][1] The molecular composition and binding epitopes of the immunoglobulin G (IgG) antibodies that circulate in blood plasma after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecti

California
United-states
San-francisco
University-of-california
Lamontagne-center
Ut-system-proteomics-network
National-institute-of-allergy
Department-of-defense
Infectious-diseases-research-program
Sauer-structural-biology-laboratory
Us-army

New Artificial Intelligence Tool May Speed Up Drug Discovery Using Images

New Artificial Intelligence Tool May Speed Up Drug Discovery Using Images New Artificial Intelligence Tool May Speed Up Drug Discovery Using Images Japanese researchers are using artificial intelligence (AI) to gain insights from cryo-electron microscopy. Artificial intelligence (AI) machine learning is transforming pharmaceutical drug discovery. Advances in deep learning, a subset of machine learning, is enabling researchers to identify patterns in fields where there are large amounts of complex data, such as imaging. In a recent study published in Nature Machine Intelligence, researchers in Japan created an AI deep neural network to extract information on protein dynamics from images captured using cryo-electron microscopy (cryo-EM).

New-york
United-states
Japan
Cambridge
Cambridgeshire
United-kingdom
Switzerland
Japanese
Shigeyuki-matsumoto
Kei-terayama
Jacques-dubochet
Takayuki-kato

The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates

Among the most promising therapeutic options for individuals with coronavirus disease 2019 (COVID-19) are monoclonal antibodies (mAbs). In this study, Jones et al . identified, characterized, and tested one such mAb, LY-CoV555, in vitro and in vivo. They found that LY-CoV555 bound to the severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) spike protein and prevented its interaction with angiotensin-converting enzyme 2. Prophylactic treatment with LY-CoV555 protected the upper and lower respiratory tracts of nonhuman primates from becoming infected with SARS-CoV-2. Together, these data support the clinical use of LY-CoV555 for treating patients with COVID-19. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less res

South-africa
China
Italy
United-states
United-kingdom
Chinese
American
K-huntington-eli-lilly
Gatan-solarus
Isoplates-perkinelmer
Eli-lilly
Oxford-cryosystems

Structural impact on SARS-CoV-2 spike protein by D614G substitution

Abstract Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

United-kingdom
Boston
Massachusetts
United-states
South-africa
Brazil
James-chou
Structural-biology-of-harvard-medical-school
Protein-data-bank
Massachusetts-consortium-on-pathogen-readiness-mass
Nancy-lurie-marks-family-foundation
Harvard-center

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