Table 1 RBD domain mutations selected by in vitro evolution for higher affinity versus those spreading in SARS-CoV-2

From: SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution

In vitro evolution

                  

RBD position*

 

358

445

446

448

460

468

470

477

478

481

483

484

490

493

494

498

501

WT residue

 

I

V

G

N

N

I

T

S

T

N

V

E

F

Q

S

Q

N

Library S2

 

F

                

Library B3

 

F

  

S

 

T

 

N

 

Y

E

K

S

   

Y

Library B4

 

F

 

R

 

K

V

 

N

S

  

K

Y

 

P

R

Y

Library B5

 

F

 

R

 

K

V

 

N

   

K

Y

H

P

R

Y

Library B6(FA)

 

F

K

  

K

T

M

N

   

K

  

P

R

Y

Clone B62

 

F

K

  

K

T

M

N

   

K

   

R

Y

SARS-CoV2 variant

Lineagea

             
 

B.1.160

   

N

         
 

B.1.1.317

   

N

         

Alpha

B.1.1.7

            

Y

Beta

B.1.351

       

K

    

Y

Gamma

P.1

       

K

    

Y

Theta

P.3

       

K

    

Y

All mutations b

     

T, (I), K, S, C

F, T, L, J, M, (V)

I, V, K, (N), R, A

I, R, G, T, K, (N)

S, A, I, R, (K), H

Y, S, (K), D, T, H

(F), A, G, L, I

Q, A, D, G, R, V, L, (K)

Y, I, R, L, V, (S)

L, (K), H, R, I, E, P

(P), L, A, R, T

H, P, F, (R), M, P, L

R, T, S, K, E, H, (Y)

  1. Amino acids in bold are dominant, that is, they account for more than 50% of selected clones; underlined amino acids are minor, that is, they account for fewer than 50% of clones at a given position. Emerging mutations that are present both in clinical samples and in yeast display experiments occur at positions 477, 484 and 501.
  2. aLineage designation by Rambaut et al.48; alternative strain designation proposed by NextStrain initiative49: 20E/EU1 (B.1.160), Alpha (B.1.1.7, 20I/501Y.V1), Beta (B.1.351, 20I/501Y.V2) and Gamma (P.1, 20I/501Y.V3).
  3. bThe most abundant mutation at a given position is shown in parentheses. Mutations that were detected by yeast display affinity maturation are in bold. Insertion–deletion mutations were not included (GISAID database (13 April 2021)).
  4. Biophysical and binding parameters of multiple selected mutants and RBDs from different virus lineages are shown in Table 2 and Fig. 2.
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