In silico evaluation of lapachol derivatives binding to the Nsp9 of SARS-CoV-2
| Autor: | Igor Rodrigues Lapa, Nilson Nicolau Junior, Renato Santana Aguiar, Mariana Sant’Anna Pereira Nicolau, Bruno Amaral Meireles, Diego Pandeló José, Ana Carolina Gomes Jardim, Igor Andrade Santos |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Nsp9
2019-20 coronavirus outbreak Coronavirus disease 2019 (COVID-19) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) In silico 030303 biophysics Molecular Dynamics Simulation Ligands World health 03 medical and health sciences chemistry.chemical_compound Viral Proteins Structural Biology Pandemic Global health Medicine Humans Molecular Biology Lapachol 0303 health sciences business.industry SARS-CoV-2 COVID-19 General Medicine lapachol derivatives Virology COVID-19 Drug Treatment Molecular Docking Simulation chemistry RNA business Research Article Naphthoquinones |
| Zdroj: | Journal of Biomolecular Structure & Dynamics article-version (VoR) Version of Record Journal of Biomolecular Structure and Dynamics |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | SARS-CoV-2 is the etiological agent of COVID-19, which represents a global health emergency that was rapidly declared a pandemic by the World Health Organization. Currently, there is a dearth of effective targeted therapies against viruses. Natural products isolated from traditional herbal plants have had a huge impact on drug development aimed at various diseases. Lapachol is a 1,4- naphthoquinone compound that has been demonstrated to have therapeutic effects against several diseases. SARS-CoV-2 non-structural proteins (nsps) play an important role in the viral replication cycle. Nsp9 seems to play a key role in transcription of the RNA genome of SARS-CoV-2. Virtual screening by docking and molecular dynamics suggests that lapachol derivatives can interact with Nsp9 from SARS-CoV-2. Complexes of lapachol derivatives V, VI, VIII, IX, and XI with the Nsp9 RNA binding site were subjected to molecular dynamics assays, to assess the stability of the complexes via RMSD. All complexes were stable over the course of 100 ns dynamics assays. Analyses of the hydrogen bonds in the complexes showed that lapachol derivatives VI and IX demonstrated strongest binding, with a stable or increasing number of hydrogen bonds over time. Our results demonstrate that Nsp9 from SARS-CoV-2 could be an important target in prospecting for ligands with antiviral potential. In addition, we showed that lapachol derivatives are potential ligands for SARS-CoV-2 Nsp9. Communicated by Ramaswamy H. Sarma |
| Databáze: | OpenAIRE |
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