Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 36, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2103154118
Keywords
SARS-CoV-2; COVID-19; emerging variants; immune evasion; antibodyresponse
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Research suggests that SARS-CoV-2 has the potential to generate variants resistant to neutralizing antibodies, and computational modeling predicts that these variants may prevent binding of neutralizing antibodies. Therefore, the development of vaccines and antibodies capable of controlling emerging variants is crucial.
To investigate the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the immune population, we coincupi bated the authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for seven passages, but, after 45 d, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough. At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed, at day 80, by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization. Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom, South Africa, Brazil, and Japan of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.
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