As SARS-CoV-2 continues to evolve, new variants are expected to arise that may have an increased ability to infect their hosts and evade the hosts’ immune systems. The first key step in infection is when the virus’s spike protein binds to the ACE2 receptor on human cells. Researchers at Penn State have created a novel framework that can predict with reasonable accuracy the amino acid changes in the virus’s spike protein that may improve its binding to human cells and confer increased infectivity to the virus.