Short communication

SARS-CoV-2 variant Omicron (B.1.1.529) is in a rising trend of mutations increasing the positive electric charge in crucial regions of the spike protein S

Piotr H. Pawłowski

Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland

An increase in the positive electric charge of SARS-CoV-2 variant Omicron (B.1.1.529) was reported and the electrostatic interaction between the spike protein S and ACE2 receptor was estimated. The results presented here suggest that electrogenic mutations in specific regions of the S protein and the electrostatic force may facilitate viral infection of the host cell.

Keywords: coronavirus; COVID-19; SARS-CoV-2; Omicron; spike protein S; amino acids; electric charge; potential energy, electrostatic interaction

Received: 08 December, 2021; revised: 08 December, 2021; accepted: 08 December, 2021; available on-line: 14 December, 2021


Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE2, Angiotensin converting enzyme 2; S, spike protein; RBD, receptor-binding domain; RBM, receptor-binding motif; S1/S2, cleavage area; aa, amino acid; D, Aspartic Acid; E, Glutamic Acid; K, Lysine; R, Arginine


The new SARS-CoV-2 B.1.1.529 variant of concern, Omicron (pdf1), detected at the beginning of November 2021, is characterized by 37 point mutations in the structural elements, four small deletions, and one small insertion. Of these, 30 missense substitutions are in the spike protein (S), with half of them in the receptor-binding domain (RBD), where 10 of them are concentrated in the receptor-binding motif (RBM). Two mutations had been found in the cleavage area (S1/S2). Eight mutations in RBD and S1/S2 refer to charged amino acids (D, E, K, R).


Data were obtained from the UK Health Security Agency technical briefings 15 (pdf2) and 29 (pdf1).

Results and Discussion

Arithmetic calculations show that charged amino acid mutations in the RBD and S1/S2 regions give a net increase in the positive charge (ΔQ= +4 [e]). Such an outcome is in line (Fig. 1) with a previously demonstrated trend of SARS-CoV-2 variants’ charge evolution (Pawłowski, 2021a).

The recently described B.1.1.529 variant causes a lot of anxiety. The consequences of detected 42 changes in the sequence of structural elements are still intensely investigated. Whether they would cause a change in the virulence of the virus still remains an open question. The resulting conformational changes may modify the lock-key interaction of RBD with the ACE2 cell surface receptor or with the host’s antibodies. Regardless of this, an increase in the positive charge at the RBD end of the S protein will increase a long-range electrostatic attraction between the spike and the negatively charged ACE2 contact zone (Fig. 2). At a distance of about 3 nm, the energy of this interaction is higher than the energy of thermal motion. Furthermore, additional charges may change multipolar interactions of the approaching molecules (Pawłowski, 2021b). They may also modify virus’s interaction with charged antibodies, e.g. in the S1/S2 cleavage area.


The above results indicate that electrogenic mutations in specific regions of the S protein and the electrostatic force may be an important weapon used by the virus when attacking cells. As a result, the Coulomb attraction between the S protein and ACE2 is greater and stronger for Omicron than the “wild-type” virus. At a distance of 1 nm, the energy difference equals 14 kBT. As an originally positive electric charge of the nucleocapsid protein has been also increased (Hodcroft, 2021) in the Omicron variant, SARS-CoV-2 deserves to be called the “electric” virus.


Hodcroft EB (2021) CoVariants: SARS-CoV-2 Mutations and Variants of Interest.

Pawłowski PH (2021a) Additional positive electric residues in the crucial spike glycoprotein S regions of the new SARS-CoV-2 variants. Infect Drug Resist 14: 5099–5105.

Pawłowski PH (2021b) Charged amino acids may promote coronavirus SARS-CoV-2 fusion with the host cell. AIMS Biophysics 8: 111–120.

pdf1. SARS-CoV-2 variants of concern and variants under investigation in England, technical briefing 29 (PDF) (Briefing). Public Health England. 26 November 2021. GOV-10481. Archived (PDF) from the original on 26 November 2021. Retrieved 26 November 2021.

pdf2. UK Health Security Agency.