In the current pandemic situation raised due to COVID-19, drug reuse is emerging as the first line of treatment. The viral agent that causes this highly contagious disease and the acute respiratory syndrome coronavirus (SARS-CoV) share high nucleotide similarity. Therefore, it is structurally
expected that many existing viral targets are similar to the first SARS-CoV, probably being inhibited by the same compounds. Here, we selected two viral proteins based on their vital role in the viral life cycle: Structure of the main protease SARS-CoV-2 and the structural base of the SARS-CoV-2
protease 3CL, both supporting the entry of the virus into the human host. The approved drugs used were azithromycin, ritonavir, lopinavir, oseltamivir, ivermectin and heparin, which are emerging as promising agents in the fight against COVID-19. Our hypothesis behind molecular coupling studies
is to determine the binding affinities of these drugs and to identify the main amino acid residues that play a fundamental role in their mechanism of action. Additional studies on a wide range of FDA-approved drugs, including a few more protein targets, molecular dynamics studies, in vitro
and biological in vivo evaluation are needed to identify combination therapy targeted at various stages of the viral life cycle. In our experiment in silico, based mainly on the molecular coupling approach, we investigated six different types of pharmacologically active drugs,
aiming at their potential application alone or in combination with the reuse of drugs. The ligands showed stable conformations when analyzing the affinity energy in both proteases: ivermectin forming a stable complex with the two proteases with values −8.727 kcal/mol for Main Protease
and −9.784 kcal/mol for protease 3CL, Heparin with values of −7.647 kcal/mol for the Main protease and −7.737 kcal/mol for the 3CL protease. Both conform to the catalytic site of the proteases. Our studies can provide an insight into the possible interactions between ligands
and receptors, through better conformation. The ligands ivermectin, heparin and ritonavir showed stable conformations. Our in-silica docking data shows that the drugs we have identified can bind to the binding compartment of both proteases, this strongly supports our hypothesis that the development
of a single antiviral agent targeting Main protease, or 3CL protease, or an agent used in combination with other potential therapies, it could provide an effective line of defense against diseases associated with coronaviruses.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
No Metrics
Keywords:
Affinity Energy;
COVID-19;
Molecular Docking;
Pharmacology;
Proteases
Document Type: Research Article
Affiliations:
1:
Laboratory of Preparation and Computation of Nanomaterials (LPCN), Federal University of Pará, C. P. 479, 66075-110 Belem, PA, Brazil
2:
Federal University of Lavras (UFLA), Chemistry Department, 37200-000 - Lavras, MG, Brazil
3:
Post-Graduation Program in Engineering of Natural Resources of the Amazon, Institute of Technology (ITEC), Federal University of Pará, C. P. 2626, 66.050-540, Belem, PA, Brazil
4:
Universidade Federal de Jataí. Rodovia BR-364, 75.8016-15 - Jataí, GO - Brazil
5:
Federal University of the South and Southeast of Pará. FL 17, QD 04, LT Especial, New Marabá, 68.505-080 - Marabá, PA - Brazil
Publication date:
01 April 2021
More about this publication?
Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
- Editorial Board
- Information for Authors
- Subscribe to this Title
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites