A recent study has uncovered that the SARS-CoV-2 virus, which causes COVID-19, uses two distinct fusion peptides in its spike protein to enter human cells. These peptides act like molecular keys, allowing the virus to fuse its membrane with that of the host cell, a crucial step in the infection process. The research, conducted by scientists at ITQB NOVA, identified two key regions within the spike protein: one at the N-terminal end and another located deeper within the protein structure. According to the study, published in the Journal of Virology, the first peptide initiates contact with the host cell membrane, while the second one inserts itself further into the membrane, causing it to destabilize and allowing the virus to enter the cell. This dual mechanism of fusion may explain the virus's high efficiency in infecting human cells. The findings were the result of a multidisciplinary effort combining computational modeling, biophysical experiments, and virology. The researchers suggest that this fusion model might be common among various coronaviruses, as these peptides appear to be conserved across different strains. This insight could be valuable for developing broader strategies to combat future coronavirus outbreaks. Understanding how the virus enters cells may lead to more effective treatments or vaccines that target these fusion mechanisms. The study was led by Diana Lousa, a researcher at ITQB NOVA, and involved collaboration with several institutions, including the Faculty of Medicine at the University of Lisbon, the Gulbenkian Institute for Molecular Medicine, and the Católica Biomedical Research Center. Their combined expertise allowed for a comprehensive analysis of the virus's infection process, offering new perspectives on how coronaviruses interact with human cells.