Researchers developed a method to identify amino acids important for the entry of viruses such as SARS-CoV-2 into human cells. They analyzed the Spike/ACE2 protein complex, which is a significant target for antivirals: the interaction between the viral Spike protein and the human ACE2 receptor facilitates viral entry. Due to mutations (changes in specific amino acids that comprise Spike), there are several Spike variants that may display interactions of varying strengths with ACE2. The researchers performed a structural analysis of the Spike/ACE2 interaction to identify amino acids that interacted the strongest between Spike and ACE2. Then, they analyzed a library of known mutations of the SARS-CoV-2 Spike protein, focusing specifically on the amino acid locations that they had found to interact the strongest, as well as mutations of human ACE2. The results enable scientists to identify how these different amino acids can change the effects of a certain disease in humans.