The new SARS-CoV-2 strain shows a stronger binding affinity to ACE2 due to N501Y mutant

Abstract

SARS-CoV-2 is a global challenge due to its ability to spread much faster than the SARS-CoV, which was attributed to the mutations in the receptor binding domain (RBD). These mutations enhanced the electrostatic interactions. Recently, a new strain is reported in the UK that includes a mutation (N501Y) in the RBD, that is possibly increasing the infection rate. Here, using Molecular Dynamics simulations (MD) and Monte Carlo (MC) sampling, we show that the N501 mutation enhanced the electrostatic interactions due to the formation of a strong hydrogen bond between SARS-CoV-2-T500 and ACE2-D355 near the mutation site. In addition, we observed that the electrostatic interactions between the SARS-CoV-2 and ACE2 in the wild type and the mutant are dominated by salt-bridges formed between SARS-CoV-2-K417 and ACE2-D30, SARS-CoV-2-K458, ACE2-E23, and SARS-CoV-2-R403 and ACE2-E37. These interactions contributed more than 40% of the total binding energies.

Keywords: Binding domains; Electrostatic interactions; Molecular dynamics; Monte Carlo; SARS-CoV; SARS-CoV-2.

Graphical abstract

Fig. 1

Salt-bridges between RBD and ACE2 in both of WT and N501Y mutated structure. The WT RBD and ACE2 are shown in Blue while the N501Y mutated RBD and ACE2 are shown in Green. (a-g) Different salt-bridges interactions (interaction energies are shown in Table.S1). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

(a) [PDB code 6M17]: SARS-CoV2 RBD and human ACE2 complex. RBD is shown in cartoon view. (b) Residues at position 501 for both of WT and N501Y mutated structures and interacting residue in the vicinity of position 501.The WT RBD and ACE2 are shown in Blue while the N501Y mutated RBD and ACE2 are shown in Green. (c) The distance in Å between OG1 of SARS-CoV-2 and ACE2-T500 and OD2 of D355 through 6 ns MD trajectory.

Fig. 3

Representation of a selected favorable Electrostatic and vdW interactions in both of WT and N501Y complexes. (Table S1).

Fig. 4

The interactions between the residue at position 501 in SARS-CoV2 RBD and nearby residues. (A) Shows interaction between mutated site Y501 in RBD and human ACE2 complex. (B), shows interaction between N501 in the native RBD and human ACE2 complex. The RBD and ACE2 are shown in Green and Blue, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)