Türk Yoğun Bakim Derneği Dergisi (Dec 2021)

Investigation of Interactions Between Sedative, Analgesic and Anaesthetic Drugs with SARS-CoV-2, ACE-2 and SARS-CoV-2- ACE-2 Complex by Molecular Docking Method

  • Evren Büyükfırat,
  • Mustafa Durgun,
  • Nuri Yorulmaz,
  • İsmail Koyuncu,
  • Mahmut Alp Karahan,
  • Ataman Gonel,
  • Veli Fahri Pehlivan

DOI
https://doi.org/10.4274/tybd.galenos.2021.69885
Journal volume & issue
Vol. 19, no. 1
pp. 8 – 32

Abstract

Read online

Objective:This study aimed to investigate the inhibitory effects of sedative, analgesic and anaesthetic drugs on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human angiotensin converting enzyme-2 (ACE-2) and SARS-CoV-2-ACE-2 complex through molecular docking and their potential use for the treatment of coronavirus disease-2019 (COVID-19).Materials and Methods:In this study, molecular docking was employed to investigate the molecular interaction between drugs under clinical tests (chloroquine, hydroxychloroquine and nelfinavir) and the most commonly used drugs for sedation, analgesia and anaesthesia, such as inhibitors (desflurane, dexmedetomidine, fentanyl, ketamine, midazolam, propofol, remifentanil and sevoflurane) of three different enzymes (6LU7, 1R4L and 6LZG). Autodock 4.2 Lamarckian Genetic Algorithm was used to analyse the probability of the molecular docking. The evaluation was based on docking points calculated by Biovia Discovery Studio Visualizer 2020. As a result of the molecular docking, interaction types, such as hydrogen-electrostatic and van der Waals between enzymes and drugs, were determined and the results were compared.Results:Among the drugs included in the study, fentanyl had a low binding energy (-8.75 to -7.64 kcal/mol) for SARS-CoV-2, ACE-2 and SARS-CoV-2-ACE-2 complex and can inhibit these proteins at low concentrations. Apart from fentanyl, midazolam, ketamine, propofol and remifentanil can also inhibit proteins; however, sevoflurane and desflurane were found to be ineffective.Conclusion:Our findings suggest that fentanyl is preferable for sedation, analgesia and anaesthesia in COVID-19 patients and that total intravenous anaesthesia can be preferred for general anaesthesia. However, experimental and clinical studies are required to determine the efficacy of these substances in treatment.

Keywords