Structural Impact of Mutation D614G in SARS-CoV-2 Spike Protein: Enhanced Infectivity and Therapeutic Opportunity

• Autores: Fernandez, Ariel
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: COVID-19; SARS-CoV-2; Biophysics; Dehydron Physics
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

With the COVID-19 pandemic, the evolutionary fate of SARS-CoV-2 becomes a matter of utmost concern. Mutation D614G in the spike (S) protein has become dominant, and recent evidence suggests it yields a more stable phenotype with higher transmission efficacy. We carry out a structural analysis that provides mechanistic clues on the enhanced infectivity. The D614G substitution creates a sticky packing defect in subunit S1, promoting its association with subunit S2 as a means to stabilize the structure of S1 within the S1/S2 complex. The results raise the therapeutic possibility of immunologically targeting the epitope involved in stabilizing the G614 phenotype as a means of reducing the infection efficacy of SARS-CoV-2. This therapeutic modality would not a-priori interfere directly with current efforts toward the immunological targeting of the RBD epitope; hence, it could be exploited as a complementary treatment.
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina