Erythromycin, Roxithromycin, Azithromycin and Clarithromycin targeting the SARS-COV-2 spike protein: a molecular dynamics study.
| dc.contributor.advisor | Faya, Andile Kennedy Mbuso. | |
| dc.contributor.author | Naidoo, Eustacia. | |
| dc.date.accessioned | 2023-11-09T07:23:23Z | |
| dc.date.available | 2023-11-09T07:23:23Z | |
| dc.date.created | 2022 | |
| dc.date.issued | 2022 | |
| dc.description | Masters Degree. University of KwaZulu-Natal, Durban. | en_US |
| dc.description.abstract | The Covid-19 global pandemic has taken the lives of many people and has left the health sector in ruins. There is a desperate need for the scientific and medical community to pose new strategies to combat this virus. One way is repurposing of already existing drugs for the safe treatment of Covid-19. In view of the above facts, the present research project work was planned and aimed to identify the mechanism of inhibition of macrolides by evaluating them in silico against the SARS-CoV-2 spike protein. We performed molecular dynamics and molecular docking studies on the following macrolide antibiotics: azithromycin, erythromycin, clarithromycin and roxithromycin, and we compared these with the results achieved from our controls (Ivermectin and Remdesivir). Our ligands were prepared using chemdraw and chimera software. Protein data bank was used to retrieve the four receptors: 3CLpro (6LU7), native human ACE2 (1R42), RdRp (6M71) and spike RBD-ACE2 (6LZG)). AutoDock Vina software was used to perform all docking experiments. Fitting analyses were performed using PyMOL and Biovia Discovery Studio. GROMACS was used for molecular dynamics studies to determine RMSD (Root Mean Square Deviation) and RMSF (Root Mean Square Fluctuation) values. We then went on to determine the intermolecular hydrogen bonding present, as well as the distances of the ligand whilst inside the pocket. Our findings revealed that all the macrolide antibiotics portrayed similar results with each other, as well as with each of our controls (Ivermectin and Remdesivir). Each of the macrolide antibiotics showed strong binding with each of the four receptors. However, azithromycin showed the greatest binding potential (-7.9 kcal/mol) relative to the two controls (Ivermectin (-10.4 kcal/mol) and Remdesivir (-8.5 kcal/mol)). Azithromycin-ACE2 complex showed the least deviation to the ACE2 protein and is therefore the most similar. The average RMSF values shows that there are potential interactions of azithromycin with the receptor protein (ACE2). Covid-19 emerged in 2019, and to this date, 2022, there is no known cures. There have been vaccines like Johnson and Johnson and Pfizer which have been tried and tested and has shown to reduce severity of disease and minimize fatality. However, due to the new emerging strains, there is a continuous need for new therapeutic interventions. Azithromycin has also showed similar results to both Ivermectin and Remdesivir (controls), showing great binding affinity for the ACE-2 receptor. Our analysis based on molecular dynamics simulation and MM-PBSA binding free energy calculation suggests that azithromycin, erythromycin, clarithromycin and roxithromycin could serve as SARS-CoV-2 inhibitors, hence an alternative solution to treat COVID-19 upon further clinical validation. | en_US |
| dc.identifier.uri | https://researchspace.ukzn.ac.za/handle/10413/22515 | |
| dc.language.iso | en | en_US |
| dc.subject.other | SARS-COV-2. | en_US |
| dc.subject.other | Coronavirus. | en_US |
| dc.subject.other | Covid-19. | en_US |
| dc.subject.other | Spike protein. | en_US |
| dc.subject.other | Azithromycin. | en_US |
| dc.subject.other | Macrolide antibiotics. | en_US |
| dc.subject.other | Viral infections. | en_US |
| dc.subject.other | Drug repurposing. | en_US |
| dc.subject.other | Pandemic. | en_US |
| dc.title | Erythromycin, Roxithromycin, Azithromycin and Clarithromycin targeting the SARS-COV-2 spike protein: a molecular dynamics study. | en_US |
| dc.type | Thesis | en_US |