Development, validation and analysis of a human profurin 3D model using comparative modeling and molecular dynamics simulations

Abstract

The emergence of new viruses can lead to the outbreak of pandemics as occurred at the end of 2019 with the coronavirus disease (or COVID-19). The fastest way to effectively control viral infections is to develop broad-spectrum antivirals that can fight at least an entire class of viruses. Profurin, the furin precursor propeptide, is responsible for the autoactivation step which is crucial for the maturation of several viral substrates. This role makes the study of furin and profurin interactions interesting for the development of new potential broad-spectrum antivirals for the treatment against several human viral diseases. Since there is no 3D model of profurin published in the literature or deposited in a database, this work reports the development, validation and analysis of a profurin 3D model using comparative modeling and molecular dynamics. The model is available in ModelArchive at https://www.modelarchive.org/doi/10.5452/ma-ct8l7. The usage of this model will make possible further studies of molecular docking and MD simulations of the profurin-furin system, in the design of new potential broad-spectrum antivirals for the treatment against several human viral diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• Profurin
• comparative modeling
• molecular dynamics
• force fields
• viral infections
• broad spectrum antivirals

Acknowledgments

The authors acknowledge funding by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) and FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro) under Grants SEI-260003/009792/2021, SEI-260003/007043/2022, and SEI-260003/003788/2022. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) under Grant Finance Code 001. This work used resources of the Centro Nacional de Processamento de Alto Desempenho em São Paulo (CENAPAD-SP).

Authors’ contributions

Brenda de Souza Ferrari: conceptualization, formal analysis, investigation, methodology, resources, software, visualization, writing—original draft. Camilo Henrique da Silva Lima: conceptualization, project administration, resources, supervision, writing—review, editing. Magaly Girão Albuquerque: conceptualization, project administration, supervision, writing—review, editing.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) under Grant Finance Code 001; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) and FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro) under Grants SEI-260003/009792/2021, SEI-260003/007043/2022, and SEI-260003/003788/2022.