IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Improving inhibition potential of an ACE2-derived peptide against SARS-CoV-2 spike protein by rational design
Autor/es:
ARRAR, MEHRNOOSH; DI LELLA, SANTIAGO; FLOREZ RUEDA, SEBASTIAN; LAUSTER, DANIEL; SARTO, CAROLINA; HACKENBERGER, CHRISTIAN
Reunión:
Congreso; XLIX Reunión Anual SAB; 2021
Institución organizadora:
SAB
Resumen:
In the recent SARS-CoV-2 pandemic, the importance of designing neutralizing strategiesfor the virus is evident. During viral infection, the spike protein is responsible for theattachment to the host cell surface via binding to angiotensin converting enzyme 2(ACE2) and for the fusion of viral and cell membranes releasing the viral genome into thecytoplasm. In this sense, some peptides are capable of competitively inhibiting theinteraction between SARS-CoV-2 and ACE2. Earlier studies of the interaction between thespike receptor binding domain (RBD) of the SARS-CoV-1 and ACE2 identifiedcharacteristic regions of the receptor, from which a derived peptide, called p6, was foundto have potent antiviral activity. In this work, we propose five new peptides derived fromACE2. Using atomistic MD simulations, we started analyzing p6, and then we rationallydesigned five new peptides using two differentstrategies: On the one hand, the hydrophobic and solvent-exposed residues were mutatedexpecting a stabilization of the secondary structure and on the other hand, we tried toimprove the interaction based on per-residue energy calculations and publishedmutationalanalysis. We compare the analysis of the computer simulations to experimentallyobtained Kd values, and highlight key factors that contribute to the tight binding of thep6 peptide to the SARS-CoV-2 RBD.