Covid-19 Pandemic
After three months shutdown of most research activities,
we have just opened up some research work. It will be a long road towards full recovery.
While we practice social distancing, remember the Earth is always a beautiful place to walk on and
our obligation to protect it for the future generations is beyond this pandemic and the next. -- 06/2020, H. Zhou
"The most incomprehensible thing about the universe is that it is comprehensible." -- Albert Einstein
"Nothing in all the world is more dangerous than sincere ignorance and conscientious stupidity." -- Martin Luther King Jr.
"In the End, we will remember not the words of our enemies, but the silence of our friends." -- Martin Luther King Jr.
"The ultimate tragedy is not the oppression and cruelty by the bad people but the silence over that by the good people." -- Martin Luther King Jr.
Progress in Molecular Biology of SARS-CoV-2
Here are some exciting new research results from work on SARS-CoV-2 virus with a focus on its structural biology.
- SARS-CoV-2 variants, spike mutations and immune escape (06/01/2021)
This review summarizes the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on
antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies
in global sequence datasets.
- Structural and functional ramifications of antigenic
drift in recent SARS-CoV-2 variants (05/20/2021)
- Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual
virus-host interactions (05/14/2021)
- Structural basis for backtracking by the SARS-CoV-2 replication–transcription complex (05/11/2021)
- Structural impact on SARS-CoV-2 spike protein by D614G substitution (04/30/2021)
- In vivo structural characterization of the SARS-CoV-2 RNA genome
identifies host proteins vulnerable to repurposed drugs (04/01/2021)
- Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin (03/05/2021)
- The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2 (03/02/2021)
- Prospective mapping of viral mutations that escape antibodies used to treat COVID-19 (02/19/2021)
Starr et al. used a yeast library that covers all mutations to the SARS-CoV-2 receptor-binding domain that do not strongly disrupt binding to the host receptor (ACE2) and mapped how these mutations
affect binding to three leading anti–SARS-CoV-2 antibodies used in treatment.
- Structure of the SARS-CoV-2 RNA-dependent RNA polymerase in the presence of
favipiravir-RTP (02/16/2021)
- Structure-guided multivalent nanobodies block SARS-CoV-2
infection and suppress mutational escape (02/12/2021)
- Structure and binding properties of Pangolin-CoV spike glycoprotein inform the
evolution of SARS-CoV-2 (02/05/2021)
- Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel
regulatory motifs and mechanisms (02/04/2021)
- Structural insights into SARS-CoV-2 proteins (01/22/2021)
- The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for
antiviral drug discovery (01/20/2021)
- Structure of SARS-CoV-2 ORF8, a rapidly evolving immune evasion protein (01/12/2021)
- Development and structural basis of a two-MAb cocktail for
treating SARS-CoV-2 infections (01/11/2021)
- Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex
Reveals an Intermediate State in Cap Synthesis (01/07/2021)
- SARS-CoV-2 structural features may explain limited neutralizing-antibody responses (01/04/2021)
- Structure-based development of human antibody cocktails against SARS-CoV-2 (12/01/2020)
- High-density lipoprotein (HDL) scavenger receptor B type 1 facilitates SARS-CoV-2 entry (11/26/2020)
- Coronavirus biology and replication: implications for SARS-CoV-2 (10/10/2020)
- The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity (09/03/2020)
80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera were investigated.
- Controlling the SARS-CoV-2 spike glycoprotein conformation (07/22/2020)
The paper examines the structure and dynamics of the two distinct modes of interaction between SARS-CoV-2 spike protein and the receptor where the
mobile receptor binding domain (RBD) from S-protein is either locked in the all-RBDs ‘down’ position or adopts ‘up’ state conformations.
The aim is to guide vaccine development and rational drug design.
- SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects (07/09/2020)
- The global and local distribution of RNA structure throughout the SARS-CoV-2 genome (07/06/2020)
- Building Blocks for COVID-19 Antiviral Drugs Identified in Rapid Study (07/01/2020)
- Emergence of SARS-CoV-2 through recombination and strong purifying selection (07/01/2020)
- Structure-based drug designing and immunoinformatics approach for SARS-CoV-2 (06/28/2020)
- Rational Design of the Remdesivir Binding Site in the RNA-dependent RNA Polymerase of SARS-CoV-2: Implications for Potential Resistance (06/26/2020)
- Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir (06/26/2020)
- Virtually Screening Antiviral Compounds Against SARS-CoV-2 Structure May Speed Up Drug And Vaccine D (06/24/2020)
- Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography (06/24/2020)
- Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease (06/19/2020)
- Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein (06/18/2020)
- Comparative analysis of coronavirus genomic RNA structure reveals conservation in SARS-like coronaviruses (06/15/2020)
- The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity (06/12/2020)
- Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 (05/27/2020)
- The sprint to solve coronavirus protein structures — and disarm them with drugs (05/15/2020)
- Structure of replicating SARS-CoV-2 polymerase (04/27/2020)
Cryo-electron microscopic structure of the SARS-CoV-2 RNA-dependent polymerase in its replicating form. The structure comprises the viral proteins nsp12, nsp8,
and nsp7, and over two turns of RNA template-product duplex.
- Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors (04/24/2020)
X-ray crystal structures of the unliganded SARS-CoV-2 main protease Mpro and its complex with a potent α-ketoamide protease inhibitor.
- Structure, Function, and Antigenicity of the SARS-CoV-2
Spike Glycoprotein (04/16/2020)
Cryo-EM structures of the SARS-CoV-2 S ectodomain trimer and key differences in biogenesis of SARS-CoV-2 spike glycoprotein
with other related proteins
- Structure of the RNA-dependent RNA polymerase from COVID-19 virus (04/10/2020)
Another great progress: A cryo-EM structure of Covid-19 virus RNA polymerase complexed with various cofactors have been determined. These results
should help design and optimize drugs to attack the viral relocation engines. Molecular modeling shed light on the mechanism of inhibiting COVID-19 virus
proliferation by one of these drugs, Remdesivir, currently being used and tested on covid-19 patients.
- Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 (04/07/2020)
- A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV (04/03/2020)
This is great progress, a major step towards rational drug design against a series of related coronaviruses. The crystal structure
of the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein (antigen) complexed with an antibody (CR3022) isolated
from a patient with SARS-CoV was solved at 3.1 Å. SARS-CoV-2 uses the same host receptor, angiotensin I converting enzyme 2 (ACE2)
as SARS-CoV that was active in 2002-2003. Although CR3022 binds SARS-CoV-2 with 100-fold lower affinity than its native
target SARS-CoV (KD ~ 1 nM), the binding modes are similar. The antibody binding epitopes of the two viruses share
over 80% sequence identity and are dominated by hydrophobic interactions. Receptor-antigen and receptor-antibody interaction surfaces are
separate, suggesting direct interference of antigen-receptor surface contact is not the mechanism of the antibody function.
It further suggests that the antibody utilizes hinged motions in the aggregated multimeric states of the spike proteins to
interfere with antigen-receptor interactions.
Crystal structure of the C-terminal domain of SARS-CoV-2 spike protein in complex with human ACE2 receptor
- Structural basis of receptor recognition by SARS-CoV-2 (03/30/2020)
Crystal structure of the receptor binding domain (RBD) of the virus spike protein complexed with the receptor
- Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 (03/27/2020)
Cryo–electron microscopy structures of full-length human receptor ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the
receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2
- Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV (03/27/2020)
- Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation (03/13/2020)
- Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (03/09/2020)
- Novel antibody epitopes dominate the antigenicity of spike glycoprotein in SARS-CoV-2
compared to SARS-CoV (03/04/2020)
- A pneumonia outbreak associated with a new coronavirus of probable bat origin (02/03/2020)
Genome sequencing and similarity to SARS-CoV
2020 Hongjun Zhou