Cell: The new coronavirus N439K variant is similar in its virability and ability to spread to wild viruses, but can bind more powerfully to human ACE2 subjects

FEBRUARY 4, 2021 /--- In a new study, an international team of researchers described the effects and molecular mechanisms of an amino acid change (N439K) in the SARS-CoV-2 hedgehog protein (S protein).
SARS-CoV-2, which carries the mutation, is both common and spreading rapidly across the globe.
study was published online January 28, 2021 in the journal Cell under the title "Cycle SARS-CoV-2 Spike N439K variants maintain fitness while evading antibody-mediated immunity".
from Cell, 2021, doi:10.1016/j.cell.2021.01.037.
the researchers found that SARS-CoV-2, which carries the mutation, is similar in virulability and transmission to wild viruses, but more likely to bind to human angiosin-converting enzyme 2 (ACE2) binds.
Importantly, they found that the mutation gave the virus serum antibodies to some people and resistance to many meso-monoclonal antibodies, including one in a combination of drugs authorized by the U.S. Food and Drug Administration (FDA).
"This means that the virus has many ways to alter the immune-explicit domain to evade immunity while retaining the ability to infect and cause disease," said Gyorgy Snell, co-author of the paper and senior director of structural biology at Vir Biotechnology.
important finding of this paper is the degree of variation found in the immune-explicit receptor binding motif on the S protein.
"Although the recent British variant B.1.1.7 and the South African variant B.1.351 have attracted more attention so far, the N439K mutation is the second most common mutation in the subject binding domain (RBD) of the S protein.
N439K mutation was first discovered in Scotland in March 2020, after which a second genealogy (B.1.258) emerged independently of the rest of Europe, which was discovered in more than 30 countries around the world by January 2021.
study also reported on the X-ray crystal structure of the N439K RBD.
analysis shows that this new mutation introduces additional interactions between the virus and the ACE2 subject," Snell said.
a single amino acid change (winteramide to lysine) can form a new point of contact with the ACE2 subject, which is consistent with a threefold increase in the combined affinity measured.
, the mutation not only improves interaction with the viral subject ACE2, but also evades antibody-mediated immunity.
" Once the researchers determined that the N439K mutation would not change virus replication, they analyzed the binding of more than 440 polyclonal antibody-positive serum samples and more than 140 monoclonal antibodies from recovering patients to see if it allowed escape from antibody-mediated immunity.
found that the binding force of some monoclonal antibodies and serum samples was significantly reduced by N439K.
importantly, the N439K mutation allows the fake virus carrying the mutation to resist the melising of a monoclonal antibody that has been approved by the FDA for emergency use as part of a dual antibody composition.
they say one way around this problem might be to use antibodies that target highly conservative bits on RBD.
Snell said, "The virus is evolving on multiple fronts, trying to evade antibody reactions."
" he points out that one of the challenges in studying SARS-CoV-2 variants is the current limited number of overall sequencing variants: more than 90 million cases of COVID-19 have been recorded, and only about 350,000 virus variants have been sequenced.
said, "It's just 0.4 percent -- just the tip of the iceberg."
highlights the need for extensive monitoring, a detailed understanding of the molecular mechanisms of mutations, and the development of treatments that prevent current and future variants from becoming resistant to treatment.
" (Bioon.com) Reference: Emma C. Thomson et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell, 2021, doi:10.1016/j.cell.2021.01.037.