Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19

The outbreak of COVID-19, the disease caused by SARS-CoV-2, continues to affect millions of people around the world. The absence of a globally distributed effective treatment makes the exploration of new mechanisms of action a key step to address this situation. Stabilization of non-native Protein-P...

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Autores principales: Fernández, Julián, Lavecchia, Martín José
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Química
Molecular dynamics
Coronavirus
Docking
Virtual screening
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/123636
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-123636
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
Molecular dynamics
Coronavirus
Docking
Virtual screening
spellingShingle Química
Molecular dynamics
Coronavirus
Docking
Virtual screening
Fernández, Julián
Lavecchia, Martín José
Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19
topic_facet Química
Molecular dynamics
Coronavirus
Docking
Virtual screening
description The outbreak of COVID-19, the disease caused by SARS-CoV-2, continues to affect millions of people around the world. The absence of a globally distributed effective treatment makes the exploration of new mechanisms of action a key step to address this situation. Stabilization of non-native Protein-Protein Interactions (PPIs) of the nucleocapsid protein of MERS-CoV has been reported as a valid strategy to inhibit viral replication. In this study, the applicability of this unexplored mechanism of action against SARS-CoV-2 is analyzed. During our research, we were able to find three inducible interfaces of SARS-CoV-2 N protein NTD, compare them to the previously reported MERS-CoV stabilized dimers, and identify those residues that are responsible for their formation. A drug discovery protocol implemented consisting of docking, molecular dynamics and MM-GBSA enabled us to find several compounds that might be able to exploit this mechanism of action. In addition, a common catechin skeleton was found among many of these molecules, which might be useful for further drug design. We consider that our findings could motivate future research in the fields of drug discovery and design towards the exploitation of this previously unexplored mechanism of action against COVID-19.
format Articulo
Articulo
author Fernández, Julián
Lavecchia, Martín José
author_facet Fernández, Julián
Lavecchia, Martín José
author_sort Fernández, Julián
title Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19
title_short Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19
title_full Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19
title_fullStr Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19
title_full_unstemmed Small molecule stabilization of non-native protein-protein interactions of SARS-CoV-2 N protein as a mechanism of action against COVID-19
title_sort small molecule stabilization of non-native protein-protein interactions of sars-cov-2 n protein as a mechanism of action against covid-19
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/123636
work_keys_str_mv AT fernandezjulian smallmoleculestabilizationofnonnativeproteinproteininteractionsofsarscov2nproteinasamechanismofactionagainstcovid19
AT lavecchiamartinjose smallmoleculestabilizationofnonnativeproteinproteininteractionsofsarscov2nproteinasamechanismofactionagainstcovid19
bdutipo_str Repositorios
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