The Role of Spike Protein Mutations in the Infectious Power of SARS‐COV‐2 Variants: A Molecular Interaction Perspective

SUMMARYThe global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission.

Download Full-text

Previous Infection Combined with Vaccination Produces Neutralizing Antibodies With Potency Against SARS-CoV-2 Variants

10.1101/2021.08.27.21262744 ◽

2021 ◽

Author(s):

F Javier Ibarrondo ◽

Christian Hofmann ◽

Ayub Ali ◽

Paul Ayoub ◽

Donald B Kohn ◽

...

Keyword(s):

Antiviral Activity ◽

Neutralizing Antibodies ◽

Spike Protein ◽

Original Sequence ◽

Neutralizing Activity ◽

Previous Infection ◽

Protein Mutations ◽

Antigenic Exposure ◽

Prior Infection ◽

Spike Sequence

SARS-CoV-2 continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants.

Download Full-text

SPIKE PROTEIN AND ITS PROTEASES ROLE IN SARS-COV-2 PATHOGENICITY AND TREATMENT; A REVIEW

Proceedings of the Shevchenko Scientific Society. Medical Sciences ◽

10.25040/ntsh2021.01.05 ◽

2021 ◽

Vol 64 (1) ◽

Author(s):

Fateme Tavakoli Far ◽

◽

Ehsan Amiri-Ardekani ◽

Keyword(s):

Blood Pressure ◽

Severe Acute Respiratory Syndrome ◽

Small Molecules ◽

Cathepsin B ◽

Host Cells ◽

Spike Protein ◽

Pressure Regulation ◽

Common Receptor ◽

The World

Since December 2019, a novel beta coronavirus has spread around the world. This virus can cause severe acute respiratory syndrome (SARS). In this study, we reviewed proteases of SARS-CoV-2 based on related articles published in journals indexed by Scopus, PubMed, and Google Scholar from December 2019 to April 2020. Based on this study, we can claim that this coronavirus has about 76% genotype similarity to SARS coronavirus (SARS-CoV). Also, similarities between these two viruses have been found in the mechanism of entry into host cells and pathogenicity. ACE 2, the angiotensin convertase enzyme 2, plays a role in the Renin-Angiotensin-Aldosterone system (RAAS) and blood pressure regulation. Some mechanisms have been reported for the role of ACE 2 in the pathogenicity of SARS-CoV-2. For example, the interaction between the ACE 2 receptor and spike protein mediated by TMPRSS2, Cathepsin B/L, and other enzymes is responsible for the entry of the virus into human cells and pathogenicity. Some host cell endosomal enzymes are necessary to cleavage coronavirus spike protein and cause binding to their common receptor. So, we conclude that molecules like antibodies or small molecules like ACE 2 antagonists and soluble ACE 2 can be used as a good therapeutic candidate to prevent SARS-CoV-2.

Download Full-text

Role of Molecular Interaction in Anisotropic Light Scattering by Liquids

The Journal of Chemical Physics ◽

10.1063/1.1840491 ◽

1967 ◽

Vol 46 (10) ◽

pp. 4090-4099 ◽

Cited By ~ 85

Author(s):

Stanisℏaw Kielich

Keyword(s):

Light Scattering ◽

Molecular Interaction

Download Full-text

There is a world beyond protein mutations: the role of non-coding RNAs in melanomagenesis

Experimental Dermatology ◽

10.1111/exd.12117 ◽

2013 ◽

Vol 22 (5) ◽

pp. 303-306 ◽

Cited By ~ 4

Author(s):

Rolf K. Swoboda ◽

Meenhard Herlyn

Keyword(s):

Non Coding Rnas ◽

Protein Mutations

Download Full-text

THE VARIATION IN THE STRUCTURE OF ERYTHROCYTE NUCLEI WITH FIXATION

The Journal of Cell Biology ◽

10.1083/jcb.14.3.445 ◽

1962 ◽

Vol 14 (3) ◽

pp. 445-458 ◽

Cited By ~ 24

Author(s):

Howard G. Davies ◽

Michael Spencer

Keyword(s):

Electron Microscope ◽

Ionic Strength ◽

Divalent Cation ◽

Volume Change ◽

Chromatin Structure ◽

Molecular Interaction ◽

Calcium Ion ◽

Volume Changes ◽

Charged Macromolecules

Observations have been made on the role of a divalent cation (calcium ion) during OsO4 fixation of nuclei of frog erythrocytes, mainly after isolation from cells. The volume of the nucleus depends partly on the molecular interaction of charged macromolecules, is controlled by the ionic strength of the medium, and hence may be used as a guide in attempts to preserve structure. When the isolation and fixation media contain 0.01 M calcium at pH 6.3 the volume changes, in the light microscope, during processing are small. When the fixative does not contain these ions, reversible volume changes occur during fixation and dehydration. The chromatin of nuclei processed with minimal volume change appears, in the electron microscope, to contain fine dots and lines about 20 to 40 A in diameter, relatively close together. The chromatin structure of nuclei in which volume changes have occurred consists of dense irregularly shaped patches, relatively far apart, and ranging in diameter from about 200 A down to the limits of visibility (20 to 30 A). It is suggested that the latter structure is a precipitation artefact.

Download Full-text

Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach

10.1101/2020.07.01.150805 ◽

2020 ◽

Author(s):

Rohit Pritam Das ◽

Manaswini Jagadeb ◽

Surya Narayan Rath

Keyword(s):

Global Health ◽

Viral Infection ◽

B Cell ◽

Molecular Interaction ◽

Vaccine Candidate ◽

Virus Disease ◽

Spike Protein ◽

Vaccine Candidates ◽

Mhc Molecules ◽

Peptide Candidate

Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.

Download Full-text

Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies

10.1101/2021.02.18.431897 ◽

2021 ◽

Author(s):

Takuya Tada ◽

Belinda M. Dcosta ◽

Hao Zhou ◽

Ada Vaill ◽

Wes Kazmierski ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Receptor Binding ◽

Binding Domain ◽

Spike Protein ◽

Receptor Binding Domain ◽

Neutralization Activity ◽

Protein Mutations ◽

Spike Proteins

AbstractMonoclonal antibodies against the SARS-CoV-2 spike protein, notably, those developed by Regeneron Pharmaceuticals and Eli Lilly and Company have proven to provide protection against severe COVID-19. The emergence of SARS-CoV-2 variants with heavily mutated spike proteins raises the concern that the therapy could become less effective if any of the mutations disrupt epitopes engaged by the antibodies. In this study, we tested monoclonal antibodies REGN10933 and REGN10987 that are used in combination, for their ability to neutralize SARS-CoV-2 variants B.1.1.7, B.1.351, mink cluster 5 and COH.20G/677H. We report that REGN10987 maintains most of its neutralization activity against viruses with B.1.1.7, B.1.351 and mink cluster 5 spike proteins but that REGN10933 has lost activity against B.1.351 and mink cluster 5. The failure of REGN10933 to neutralize B.1.351 is caused by the K417N and E484K mutations in the receptor binding domain; the failure to neutralize the mink cluster 5 spike protein is caused by the Y453F mutation. The REGN10933 and REGN10987 combination was 9.1-fold less potent on B.1.351 and 16.2-fold less potent on mink cluster 5, raising concerns of reduced efficacy in the treatment of patients infected with variant viruses. The results suggest that there is a need to develop additional monoclonal antibodies that are not affected by the current spike protein mutations.

Download Full-text