13 Jul 2020

Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020(1,2). Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here Corti and Veeler et. al. describe several monoclonal antibodies that target the S glycoprotein of SARS-CoV-2, which they identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, they show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirussubgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodies that we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

7 Jul 2020

Structure of the full SARS-CoV-2 RNA genome in infected cells

SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs or vaccines with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on predicted RNA structures in SARS-CoV-2 and most putative regulatory sequences are uncharacterized. Here we report the secondary structure of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq). Silvi Rouskin et al. reveal previously undescribed structures within critical regulatory elements such as the genomic transcription-regulating sequences (TRSs). Contrary to previous studies, their in-cell data show that the structure of the frameshift element, which is a major drug target, is drastically different from prevailing in vitro models. The genomic structure detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.

7 Jul 2020

Map of SARS-CoV-2 spike epitopes not shielded by glycans

The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, Gerhard Hammer et al. performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, they recover known epitopes on S and reveal promising epitope candidates for vaccine development. They find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.

15 Aug 2019

Potential of cryo-EM for high-resolution structural analysis of gap junction channels

The review by Oshima et. al. in Current Opinions in Structural Biology outlines structural biology of gap junction channels utilizing crystallography and single-particle cryo-EM to shed light on the functional mechanisms of cell-cell communication that are essential for multicellular organisms.

15 Aug 2019

Molecular dynamics simulations of macromolecular crystals

The paper of David Case and David Cerutti in WIREs Computational Molecular Science evaluates past fusions of simulations and crystallography and looks ahead to the ways that simulations of crystal structures will enhance structural biology in the future.

14 Aug 2019

Combining Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) Spectroscopy for Integrative Structural Biology of Protein–RNA Complexes

In this publication Fred Allain et.al. reviews recent advances in hybrid structural approaches with a focus on combining MS analysis of cross-linked protein–RNA complexes and NMR spectroscopy.

12 Aug 2019

Quo Vadis Biomolecular NMR Spectroscopy?

In Quo Vadis Biomolecular NMR Spectroscopy? Phil Selenko reviews recent methodological spin-off applications whose developments were stimulated by cellular NMR approaches.

8 Aug 2019

Essay on Biomembrane Structure

Christoph Gerle provides historical outline of how we arrived at our current understanding of biomembranes and the models we use to describe them in Essay on Biomembrane Structure. A selection of direct experimental findings on the nano-scale structure of biomembranes is taken up to discuss their physical nature, and special emphasis is put on the surprising insights that arise from atomic scale descriptions.

5 Aug 2019

Role of integrative structural biology in understanding transcriptional initiation

Role of integrative structural biology in understanding transcriptional initiation is discussed by Philip Robinson et. al. in a review, which presents a general background to integrative structural biology, describes of how it should be practically implemented, and shows how it has furthered our understanding of the biology of large transcriptional assemblies. 

5 Aug 2019

Frontiers in Cryo Electron Microscopy of Complex Macromolecular Assemblies

In this publication Sriram Subramaniam et. al. report on structural studies of G protein–coupled receptors, spliceosomes, and fibrillar specimens and illustrate the progress made by advanced cryo-EM methods.

1 Aug 2019

The evolution of solution state NMR pulse sequences through the ‘eyes’ of triple-resonance spectroscopy

Lewis Kay in The evolution of solution state NMR pulse sequences through the ‘eyes’ of triple-resonance spectroscopy highlights how pulse sequence ‘engineering’ has evolved during past decades with the focus on liquid state NMR applications.