Structural Impact of Mutation D614G in SARS-CoV-2 Spike Protein: Enhanced Infectivity and Therapeutic Opportunity
| Autor: | Ariel Fernández |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
CIENCIAS MÉDICAS Y DE LA SALUD
Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Protein subunit Biotecnología relacionada con la Salud Biophysics Biology medicine.disease_cause 01 natural sciences Biochemistry Epitope Biotecnología de la Salud Viewpoint Drug Discovery medicine purl.org/becyt/ford/3.4 [https] Infectivity Mutation 010405 organic chemistry SARS-CoV-2 Organic Chemistry Spike Protein COVID-19 Phenotype 0104 chemical sciences Cell biology 010404 medicinal & biomolecular chemistry Dehydron Physics purl.org/becyt/ford/3 [https] |
| Zdroj: | ACS Medicinal Chemistry Letters CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| ISSN: | 1948-5875 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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