Article ; Online: Early combination treatment with existing HIV antivirals: an effective treatment for COVID-19?
European review for medical and pharmacological sciences
2021 Volume 25, Issue 5, Page(s) 2435–2448
Abstract: Objective: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19).: Materials and methods: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and ...
| Abstract | Objective: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19). Materials and methods: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (PDB ID: 7BV2) both available from Protein Data Bank were used in the study. Automated Docking by using blind and standard method both on Mpro and RdRp bound to the modified template-primer RNA was performed with AutoDock 4.2.6 program suite. Lamarckian genetic algorithm (LGA) was used for structures docking. All inhibitors were docked with all bonds completely free to rotate. Results: Our molecular docking findings suggest that lopinavir, ritonavir, darunavir, and atazanavir activated interactions with the key binding sites of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) protease with a better inhibition constant (Ki) for lopinavir, ritonavir, and darunavir. Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions. In principle, the four antiviral nucleotides might be used effectively against SARS-CoV-2. Conclusions: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19. |
|---|---|
| MeSH term(s) | Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antiviral Agents/pharmacology ; Atazanavir Sulfate ; COVID-19/drug therapy ; Darunavir ; Drug Combinations ; Drug Therapy, Combination/methods ; Early Medical Intervention ; Emtricitabine ; Humans ; Lamivudine ; Lopinavir ; Molecular Docking Simulation ; Nucleosides/therapeutic use ; Protease Inhibitors/therapeutic use ; Ritonavir ; SARS-CoV-2 |
| Chemical Substances | Antiviral Agents ; Drug Combinations ; Nucleosides ; Protease Inhibitors ; Lopinavir (2494G1JF75) ; Lamivudine (2T8Q726O95) ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Atazanavir Sulfate (4MT4VIE29P) ; Emtricitabine (G70B4ETF4S) ; Ritonavir (O3J8G9O825) ; Alanine (OF5P57N2ZX) ; Darunavir (YO603Y8113) |
| Language | English |
| Publishing date | 2021-03-21 |
| Publishing country | Italy |
| Document type | Journal Article |
| ZDB-ID | 605550-3 |
| ISSN | 2284-0729 ; 1128-3602 ; 0392-291X |
| ISSN (online) | 2284-0729 |
| ISSN | 1128-3602 ; 0392-291X |
| DOI | 10.26355/eurrev_202103_25285 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 1887: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.