Seasonal variation of the composition of essential oils from Piper cernuum Vell and Piper rivinoides Kunth, ADMET study, DFT calculations, molecular docking and dynamics studies of major components as potent inhibitors of the heterodimer methyltransferase complex NSP16-NSP10 SARS COV-2 protein

Abstract

Coronavirus disease (COVID-19) has the virus that causes the SARS-CoV-2 severe acute respiratory syndrome, which has reached a pandemic proportion, with thousands of deaths worldwide already registered. It has no standardized effective clinical treatment, arousing the urgent need for the discovery of bioactive compounds for the treatment of symptoms of COVID-19. In this context, the present study aimed to evaluate the influence of seasonality on the yield and chemical composition of the essential oils of Piper cernuum and Piper rivinoides as well as to evaluate the anti-SARS-CoV-2 potential of the major components of each oil by molecular docking and quantum chemical calculation (Density Functional Theory method), being possible indicate that the winter and autumn periods, the seasons of the year where it is possible to obtain the highest percentage of Piper cernuum and Piper rivinoides oils, respectively. Regarding the anti-SARS-Cov-2 potential, the present work showed that the dihydroagarofuran present in Piper cernuum, presented a strong interaction with amino acid residues from Mpro, presenting a potential similar to Remdesivir, a drug for clinical use. Regarding methyltransferase, dihydroagarofuran (Piper cernuum) and myristicin (Piper rivinoids) showed better affinity, with important interactions at the active site of the inhibitor Sinefugin, suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2. Molecular docking and molecular dynamics studies represent an initial step, being indicative for future in vitro studies of dihydroagarofuran and myristicin, as possible pharmacological tools for COVID-19.

Communicated by Ramaswamy H. Sarma

Highlights

• Autumn and winter are the most suitable seasons of the year to extract the oils of Piper rivinoides and Piper cernuum respectively.

• in silico evaluation of majoritary compounds of essential oils against the anti-SARS-Cov-2 potential by Molecular docking.

• The electronic properties were computed using the Density Functional Theory method to understand the interaction of the molecules and the amino acids.

• Dihydroagarofuran (Piper cernuum) and myristicin (Piper rivinoids) suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2.

• Dihydroagarofuran present in Piper cernuum suggesting a potential inhibitory effect of the Mpro.

Keywords:

• Essential oils
• COVID-19
• Piper
• SARS-CoV-2
• in silico
• seasonality
• Density Functional Theory
• Molecular Electrostatic Potential

Acknowledgments

The authors thank the Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (Funcap), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support and the scholarship. Francisco Wagner Q. Almeida-Neto thanks CNPq for his grant. The authors also thanks Centro Nacional de Processamento de Alto Desempenho (CENAPAD) of the Federal University of Ceará (UFC) for providing computational resources.

Authors’ contributions

Writing—Original Draft preparation: Linkoln Alves Borges Leal and Antonio Marcia Machado Marinho; Methodology and investigation: Camila Fonseca Bezerra, Andressa Kelly Ferreira e Silva, Luiz Everson da Silva, Francisco Wagner de Queiroz Almeida-Neto, and Lucas Lima Bezerra; Writing—Review & Editing, Software: Emanuelle Machado Marinho, Matheus Nunes da Rocha; Conceptualization, Resources: Carla Freire Celedonio Fernandes, Humberto Medeiros Barreto; Formal analysis, Validation, Resources: Henrique Douglas Melo Coutinho, Ana Rafaela Freitas Dotto, Wanderlei do Amaral; Formal analysis, Supervision, Conceptualization: Hélcio Silva dos Santos; Supervision, Conceptualization: Emmanuel Silva Marinho and Pedro de Lima-Neto.

Availability of supporting data

All the data generated and discussed during this work are included in this published article and in the supplementary information file.

Disclosure statement

All the authors declare that they have no competing interests.

Ethics approval and consent to participate

The experimental protocols were approved by the Ethics Committee on the use of animals at the State University of Ceará (CEUA-UECE). This article does not contain any studies with human participants.

Additional information

Funding

Hélcio Silva dos Santos acknowledges financial support from the PQ-BPI/FUNCAP (Grant#: BP4-0172-00075.01.00/20). Carla F.C. Fernandes thanks the financial support received from project Inova Fiocruz FUNCAP (Grant#: 06481104-2020).