Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species.

Immunity
Ruoke WangLinqi Zhang

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge during the global pandemic and may facilitate escape from current antibody therapies and vaccine protection. Here we showed that the South African variant B.1.351 was the most resistant to current monoclonal antibodies and convalescent plasma from coronavirus disease 2019 (COVID-19)-infected individuals, followed by the Brazilian variant P.1 and the United Kingdom variant B.1.1.7. This resistance hierarchy corresponded with Y144del and 242-244del mutations in the N-terminal domain and K417N/T, E484K, and N501Y mutations in the receptor-binding domain (RBD) of SARS-CoV-2. Crystal structure analysis of the B.1.351 triple mutant (417N-484K-501Y) RBD complexed with the monoclonal antibody P2C-1F11 revealed the molecular basis for antibody neutralization and escape. B.1.351 and P.1 also acquired the ability to use mouse and mink ACE2 receptors for entry. Our results demonstrate major antigenic shifts and potential broadening of the host range for B.1.351 and P.1 variants, which poses serious challenges to current antibody therapies and vaccine protection.

References

Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jun 20, 2020·Nature·Davide F RobbianiMichel C Nussenzweig
Jul 15, 2020·Science·Meng YuanIan A Wilson
Jul 30, 2020·The New England Journal of Medicine·Kizzmekia S CorbettBarney S Graham
Oct 13, 2020·Nature·Christopher O BarnesPamela J Bjorkman
Oct 28, 2020·Nature·Jessica A PlantePei-Yong Shi
Oct 29, 2020·The New England Journal of Medicine·Peter ChenUNKNOWN BLAZE-1 Investigators
Nov 12, 2020·Science·Bas B Oude MunninkMarion P G Koopmans
Dec 11, 2020·The New England Journal of Medicine·Fernando P PolackUNKNOWN C4591001 Clinical Trial Group
Dec 12, 2020·Cell Host & Microbe·Drew WeissmanDavid C Montefiori
Dec 18, 2020·The New England Journal of Medicine·David M WeinreichUNKNOWN Trial Investigators
Dec 31, 2020·The New England Journal of Medicine·Lindsey R BadenUNKNOWN COVE Study Group
Jan 2, 2021·Science·Kai Kupferschmidt
Jan 13, 2021·Nature Communications·Jiwan GeLinqi Zhang
Jan 22, 2021·JAMA : the Journal of the American Medical Association·Robert L GottliebDaniel M Skovronsky
Jan 31, 2021·Lancet·Ester C SabinoNuno R Faria
Feb 2, 2021·Nature·Annette B VogelUgur Sahin
Feb 4, 2021·Nature Medicine·Houriiyah TegallyTulio de Oliveira
Feb 11, 2021·Emerging Infectious Diseases·Fabrizio MaggiGianni Bonelli
Feb 11, 2021·Emerging Infectious Diseases·Takahisa FujinoNorio Ohmagari
Feb 11, 2021·Nature·Zijun WangMichel C Nussenzweig
Mar 9, 2021·Nature·Pengfei WangDavid D Ho
Mar 18, 2021·The New England Journal of Medicine·Kai WuDarin K Edwards

❮ Previous
Next ❯

Citations

Aug 11, 2021·The Journal of Clinical Investigation·Ralf DuerrAdriana Heguy
Sep 15, 2021·Briefings in Bioinformatics·Wenyang ZhouQinghua Jiang
Sep 2, 2021·Biosafety and Health·Rui-Ting Li, Cheng-Feng Qin
Sep 19, 2021·Nature Reviews. Genetics·Kaiming TaoRobert W Shafer

❮ Previous
Next ❯

Software Mentioned

PHASER (
CCP4 Program Suite
COOT
Graphpad Prism
Biacore Evaluation
FlowJo
PyMOL
Biacore Insight Evaluation
GraphPad
Chimera

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.