Dual Perspectives on the Evolution of SARS-CoV-2 Receptor Binding Domain

Jiří Zahradník¹, Miguel Padilla Blanco^1,2, Prokopios Andrikopoulos¹

¹1^st Faculty of Medicine, Charles University, BIOCEV, Prague 252 50, Czechia

² Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain

jiri.zahradnik@lf1.cuni.cz

The SARS-CoV-2 virus doesn't need a lengthy introduction. We all are aware of it and feel that nothing can surprise us anymore. With more than 16.5 million deposited sequences in the GISAID database and over 4 thousand structures in the PDB, it is by far the most extensively studied virus (20.2.2024). Still, many questions remain unanswered. In my lecture, I will show how the receptor-binding domain is shaped by evolutionary pressures to maintain high binding affinity and escape neutralizing antibodies, and how this interplay continues to surprise us with an ever-changing cooperativity landscape as can be seen from affinities in Table 1. In the second part of the lecture, we will focus on elucidating the change in tropism in SARS-CoV-2 and which structural aspects have contributed to this phenomenon.

Table 1. The ever-changing cooperativity landscape demonstrated by affinities [nM] and their impact on different SARS-CoV-2 lineages.

	R403K	V445H	N450D	L452W	N481K	V483del
WT	0.7	0.8	0.6	0.6	1.0	0.3
BA.2	2.5	0.7	0.9	0.7	0.8	0.4
XBB	1.4	1.0	0.9	1.0	0.8	0.4
XBB.1.5	1.5	0.8	1.0	0.9	0.7	0.5
BA.2.86	0.5	1.0	0.7	1.1	1.6	1.8

„The project National Institute of virology and bacteriology (Programme EXCELES, ID Project No. LX22NPO5103) - Funded by the European Union - Next Generation EU.“