3 mutations let SARS-CoV-2 to evade response of highly neutralizing COVID-19 convalescent plasma

Emanuele Andreano1 , Giulia Piccini2 , Danilo Licastro4 , Lorenzo Casalino5 , Nicole V. Johnson6 , Ida Paciello1 , Simeone Dal Monego4 , Elisa Pantano1 , Noemi Manganaro1 , Alessandro Manenti2,3 , Rachele Manna2 , Elisa Casa2,3, Inesa Hyseni2,3, Linda Benincasa3 , Emanuele Montomoli2,3,7 , Rommie E. Amaro5 , Jason S. McLellan6 , Rino Rappuoli1,8,*

doi: https://doi.org/10.1101/2020.12.28.424451

ABSTRACT 

To investigate the evolution of SARS-CoV-2 in the immune population, we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient. The plasma fully neutralized the virus for 7 passages, but after 45 days, 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 and South Africa 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. 

https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1.full.pdf