Fig. 4

Mutations in the SARS-CoV-2 replication complex (nsp7, nsp8 and nsp12) and spike glycoprotein (S). a Active form of RNA-dependent RNA polymerase (nsp12) associated with the cofactors nsp7 and nsp8 (cryo-EM structure, PDB id 6yyt) [26]. b View of the proximity surrounding the loop where site 323 of nsp12 is located to nsp8 (red box). Pro³²³Leu is a frequent mutation in nsp12. View of the proximity between Ser²⁵ in nsp7 and Asp¹⁶³ in nsp8 (green box), which likely interact with each other via hydrogen bonds. The mutation Ser²⁵Leu in nsp7 is fairly frequent. c Cryo-EM structure of the S trimer in the closed conformation showing the location of sites 614 (at end of S1 subunit, red square) and 483 (at the β-4,5 loop of the receptor-binding domain, orange square). The cryo-EM structure (PDB id 6vxx) was used in this image. Glycans are not depicted for clarity. The missing loops were modeled using the Rosetta framework [32, 72]. d Magnified view of the salt bridge network around Asp⁶¹⁴ (red box), which may facilitate electrostatic-driven interactions within monomers. The mutation Asp⁶¹⁴Gly is quite frequent (62% of sequences analyzed have it) (PDB id 6xr8) [73]. Magnified view of the interface between the spike RBD (pink) and ACE2 (orange) (orange box, PDB id 6 m17 [74]). Site 483 is located at the β-4,5 loop of RBD. The mutations Val⁴⁸³Gly, Val⁴⁸³Ala, and Val⁴⁸³Asp were identified in SARS-CoV-2