Table 1.
Details of revised studies.
| References | Method | Drugs | Results |
|---|---|---|---|
| Park S.J. et al., 2020 [30] |
In vivo (animal model) |
Lopinavir/ritonavir, Hydroxychloroquine sulfate, Emtricitabine-Tenofovir | Reduced overall clinical symptoms and not significantly diminished respiratory or gastrointestinal SARS-CoV-2 titers |
| Arshad U. et al., 2020 [31] |
In vitro Vero cells in available literature |
Lopinavir, Ritonavir | In lung tissue: Cmax/EC50 > 10: Hydroxychloroquine, Atazanavir, Chloroquine, Tipranavir, Mefloquine, Ivermectin, Azithromycin, Lopinavir; In plasma: Cmax/EC50 > 1: Nelfinavir, Chloroquine, Remdesivir, Lopinavir (Ritonavir boosted), Eltrombopag, Hydroxychloroquine, Atazanavir (Ritonavir boosted), Indomethacin, Favipiravir, Sulfadoxine, Niclosamide, Mefloquine, Tipranavir (Ritonavir boosted), Ritonavir, Merimepodib, Anidulafungin, Nitazoxanide 1< Cmax/EC90 < 2: Anidulafungin, Lopinavir, Chloroquine, Ritonavir |
| Cattaneo D. et al., 2020 [33] |
In vitro IC90 estimation |
Lopinavir | Lopinavir IC50: 26 μM Lopinavir IC90:234 μM Lopinavir Protein-adjust IC90in plasma: 4680 μM Lopinavir Protein-adjust IC90 in epithelial lining fluid: 393 μM Lopinavir Protein-adjust IC90 in cerebrospinal fluid: 58,500 μM |
| Choy K.T. et al., 2020 [32] |
In vitro Vero E6 cells |
Remdesivir, Lopinavir | To the reduction in viral RNA copy: EC50Lopinavir: 26.1 μM |
| Kang C.K. et al., 2020 [34] |
In vitro Kidney Vero cells |
Lopinavir, Ritonavir | Concentration groups tested:
|
| De Meyer S. et al., 2020 [35] |
In vitro Caco-2 cells |
Darunavir | Visual Cytopathogenic Effect-read out EC50: Darunavir: > 100 μM 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method EC50: Darunavir: > 100 μM Cytotoxic concentration causing death to 50% (CC50): Darunavir: >100 μM |
| Das S. et al., 2020 [36] |
In silico Blind molecular docking analyses with Mpro |
Commercially available compounds | Free binding energy for SARS-CoV-2 protease: Lopinavir ΔG: – 9.00 kcal/mol Ritonavir ΔG: - 9.52 kcal/mol |
| Beck B.R. et al., 2020 [44] |
In silico Molecular dynamic simulation |
Commercially available compounds | Drug-target interaction (DTI) prediction results against COVID-19's helicase: Lopinavir: 78.49 nM Ritonavir: 41.60 nM Darunavir: 90.38 nM |
| Khan S.A. et al., 2020 [49] |
In silico Molecular dynamic simulation |
Commercially available compounds | Free binding energy for SARS-CoV-2 protease by MM (GB/PB)SA method: Darunavir: - 48.1041 kcal/mol |
| Muralidharan N. et al., 2020 [37] |
In silico Molecular dynamic simulation |
Commercially available compounds | Free binding energy for SARS-CoV-2 protease: Lopinavir: - 4.1 kcal/mol Oseltamivir: - 4.65 kcal/mol Ritonavir: - 5.11 kcal/mol Lopinavir/Oseltamivir: - 5.4 kcal/mol Lopinavir/Oseltamivir/Ritonavir: - 8.32 kcal/mol |
| Nutho B. et al., 2020 [38] | In silico - Molecular dynamic simulation | Lopinavir and Ritonavir | Free binding free energy (ΔGbind) for SARS-CoV-2 protease by MM/PBSA: Lopinavir: - 10.89 ± 1.89 kcal/mol Ritonavir: - 14.93 ± 1.83 kcal/mol Binding free energy (ΔGbind) for SARS-CoV-2 protease by MM/GBSA: Lopinavir: - 13.83 ± 1.91 kcal/mol Ritonavir: - 27.78 ± 1.82 kcal/mol |
| Ortega J.T. et al., 2020 [45] |
In silico Molecular dynamic simulation |
Commercially available compounds | Free binding energy for SARS-CoV-2 protease: Lopinavir: −9.1 kcal/mol |
| Pant S. et al., 2020 [39] |
In silico Molecular dynamic simulation |
Commercially available compounds | Binding free energy (ΔGbind) for SARS-CoV-2 protease by MM/GBSA: Ritonavir: −87.24 kcal/mol Lopinavir: −73.33 kcal/mol Darunavir: −69.20 kcal/mol Docking Score: Ritonavir: −8.878 Lopinavir: −8.358 Darunavir: −7.208 |
| Peele K.A. et al., 2020 [40] |
In silico Molecular dynamic simulation |
Commercially available compounds | Docking score using GLIDE module: Lopinavir: −9.918 Darunavir: −8.843 |
| Mahanta S. et al., 2020 [48] |
In silico Molecular dynamic simulation |
Commercially available compounds | -CDocker Energy for SARS-CoV-2 protease: Lopinavir −62.07 kcal/mol Ritonavir −65.73 kcal/mol |
| Shah B. et al., 2020 [41] |
In silico Molecular dynamic simulation |
Commercially available compounds | Docking score from interaction with different COVID-19 structures as 5R7Y, 5R7Z, 5R80, 5R81 5R82: Lopinavir: - 6.834, −6.968, −7.331, −8.44, −7.58 Ritonavir: −7.621, -, −6.736, −6.764, −7.316 |
| Chen Y.W. et al., 2020 [46] |
In silico Molecular dynamic simulation |
Commercially available compounds | Binding energy for chain A active site of SARS-CoV-2 protease: Mean score: −8.2 kcal/mol Ritonavir: −7.9 kcal/mol Lopinavir: −8.0 kcal/mol Binding energy for chain B active site of SARS-CoV-2 protease: of SARS-CoV-2 protease: Mean score: −7.1 kcal/mol Ritonavir: −6.9 kcal/mol Lopinavir: −6.8 kcal/mol |
| Wang Q. et al., 2020 [47] |
In silico Molecular dynamic simulation |
Commercially available compounds | Free binding energy for SARS-CoV-2 protease: Darunavir: - 11.1 kcal/mol Ritonavir: −11.8 kcal/mol Lopinavir: −11.9 kcal/mol |
| Mamidala E. et al., 2020 [42] |
In silico Molecular dynamic simulation |
Commercially available compounds | Free binding energy for SARS-CoV-2 protease: Lopinavir: −6.11 kcal/mol Ritonavir: −8.25 kcal/mol |
| Gupta S. et al., 2020 [43] |
In silico Molecular dynamic simulation |
Literature available compounds | Binding energy raging: Lopinavir: > - 5.70 kcal/mol Range of predicted IC50 values: Standard compound(Lopinavir): 15.7–21.3 μM The total interaction energy of protein-ligand complex: Lopinavir- Mpro: −181.795 ± 13.5 kJ/mol Toxicological profile (PLD50): Lopinavir: 5000 mg/kg body weight |
|
In silico Molecular dynamic simulation |
Darunavir | Docking score range of Darunavir: – 8.6 to - 8.2 Very few interactions of Darunavir with the active site of the protease |