RESUMO
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for viral infection. The interaction of its receptor-binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2) protein is required for the virus to enter the host cell. We identified RBD binding sites to block its function with inhibitors by combining the protein structural flexibility with machine learning analysis. Molecular dynamics simulations were performed on unbound or ACE2-bound RBD conformations. Pockets estimation, tracking and druggability prediction were performed on a large sample of simulated RBD conformations. Recurrent druggable binding sites and their key residues were identified by clustering pockets based on their residue similarity. This protocol successfully identified three druggable sites and their key residues, aiming to target with inhibitors for preventing ACE2 interaction. One site features key residues for direct ACE2 interaction, highlighted using energetic computations, but can be affected by several mutations of the variants of concern. Two highly druggable sites, located between the spike protein monomers interface are promising. One weakly impacted by only one Omicron mutation, could contribute to stabilizing the spike protein in its closed state. The other, currently not affected by mutations, could avoid the activation of the spike protein trimer.
RESUMO
We report a case of prenatal diagnosis of thrombosis of the torcular Herophili. Detection at 22 weeks' gestation by ultrasound scan of an anechoic mass located immediately above the tentorium led to magnetic resonance imaging (MRI) being performed at 28 weeks which established the diagnosis of an isolated thrombosis of the torcular Herophili. MRI remained stable throughout pregnancy, and postnatal MRI confirmed the diagnosis at 2.5 months of age. The child is now 16 months old and developing normally.