Evolution to increased positive charge on the viral spike protein may be part of the adaptation of SARS-CoV-2 to human transmission

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, continues to evolve and infect individuals. The exterior surface of the SARS-CoV-2 virion is dominated by the spike protein and the current work examined spike protein biochemical features that have changed during the 2 years that SARS-CoV-2 has infected humans. These biochemical properties may influence virion survival and promote movement through the environment and within the human airway to reach target cells to bind, enter and establish the next round of infection. In addition to selective pressure to avoid immune recognition of viral proteins, we hypothesised that SARS-CoV-2 emerged from an animal reservoir capable of human infection and transmission but in a sub-optimum state and a second level of selective pressure is acting on these biochemical features. Our analysis identified a striking change in spike protein charge, from -8.3 in the original Lineage A and B viruses to -1.26 in the current Omicron viruses. In summary, we conclude that in addition to immune selection pressure, the evolution of SARS-CoV-2 has also altered viral spike protein biochemical properties. Future vaccine and therapeutic development should also exploit and target these biochemical properties.