PT  - JOURNAL ARTICLE
AU  - Jiří Zahradník
AU  - Shir Marciano
AU  - Maya Shemesh
AU  - Eyal Zoler
AU  - Jeanne Chiaravalli
AU  - Björn Meyer
AU  - Orly Dym
AU  - Nadav Elad
AU  - Gideon Schreiber
TI  - SARS-CoV-2 RBD <em>in vitro</em> evolution follows contagious mutation spread, yet generates an able infection inhibitor
AID  - 10.1101/2021.01.06.425392
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.06.425392
4099  - http://biorxiv.org/content/early/2021/01/06/2021.01.06.425392.short
4100  - http://biorxiv.org/content/early/2021/01/06/2021.01.06.425392.full
AB  - SARS-CoV-2 is constantly evolving, with more contagious mutations spreading rapidly. Using in vitro evolution to affinity maturate the receptor-binding domain (RBD) of the spike protein towards ACE2, resulted in the more contagious mutations, S477N, E484K, and N501Y to be among the first selected. This includes the British and South-African variants. Plotting the binding affinity to ACE2 of selected RBD mutations against their incidence in the population shows a strong correlation between the two. Further in vitro evolution enhancing binding by 600-fold provides guidelines towards potentially new evolving mutations with even higher infectivity. Yet, the high-affinity RBD is also an efficient drug, inhibiting SARS-CoV-2 infection. The 2.9Å Cryo-EM structure of the high-affinity complex, including all rapidly spreading mutations provides structural basis for future drug development.Competing Interest StatementThe authors J.Z. and G.S. declare the US Provisional Patent Application No. 63/125,984 (Yeda Ref.: 2020-091).