Piotr H Pawłowski Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, PolandCorrespondence: Piotr H Pawłowski Tel +48-22-659-70-72Email piotrp@ibb.waw.plAbstract: The change in the formal charge of 34 SARS-CoV-2 lineages from September 2020 to June 2021 was analyzed according to the monthly evidence of the European agency. The reported point mutations and small insertions are electrically neutral (17), positive (12), or negative (3). They had been found in the spike glycoprotein S, in the RBD and S1/S2 regions, crucial for initiation of viral infection. The most often observed were positive mutations, especially D614G and E484K, located in the region of S1/S2 junction, and in the receptor-binding domain (RBD), respectively. They are related to G and A switching. Positive mutations are stretching equally in both areas, but in the RBD region, they are more dispersed. In the set of analyzed virus variants, the increasing tendency in the number of positively charged residues in spike protein was observed. Furthermore, the well-documented WHO classes show an increase in the COVID-19 percentage case fatality with the positive increase in the spike crucial region’s total charge. The data mining, applying classifier algorithm based on the artificial neuronal network, confirms that the value and the distribution of additional positive charge in S may be important factors enabling virus impact to immunity. This may be promoted by the stronger long-range electrostatic attraction of the virus particle to the host cell, preceding the infection. The estimation of the potential energy for the RBD approaching the angiotensin-converting enzyme (ACE2) was presented.Keywords: coronavirus, COVID-19, SARS-CoV-2, spike protein S, amino acids, charge, potential energy, electrostatic interactions