Table 5.
FDA approved drugs or compound in clinical trial selected from PPI-based drug repurposing with in vitro and/or in vivo efficacy.
| Drug | Chemical Structure | Mechanism of Action | SARS-CoV-2 PPI | Studies Which Detected Virus–Host PPI | In Vitro SARS-CoV-2 Antiviral Effects | In Vivo SARS-CoV-2 Activity |
|---|---|---|---|---|---|---|
| Chlorpromazine FDA approved |
|
Ligand of Sigma-1 receptor | Nsp6-Sigma-1 (1) | Gordon et al. [17] Stukalov et al. [21] Laurent et al. [24] |
A549-ACE2 pIC50 = 6.05 |
Reduced requirement to mechanical ventilation (2) |
| Fluphenazine FDA approved |
|
Ligand of Sigma-1 receptor | Nsp6-Sigma-1 (1) | Gordon et al. [17] Stukalov et al. [21] Laurent et al. [24] |
A549-ACE2 pIC50 = 6.46 |
Reduced requirement to mechanical ventilation (2) |
| Haloperidol FDA approved |
|
Ligand of Sigma-1 receptor | Nsp6-Sigma-1 (1) | Gordon et al. [17] Stukalov et al. [21] Laurent et al. [24] |
A549-ACE2 pIC50 = 5.68 |
Reduced requirement to mechanical ventilation (2) |
| Indomethacin FDA approved |
|
PGES-2 inhibitor | Nsp7-PGES-2 (3) | Gordon et al. [17] Gordon et al. [18] |
A549-ACE2 pIC50 = 4.25 |
Reduced hospitalization (4) |
| Ipatasertib compound in clinical trial |
|
AKT inhibitor a potential kinase phosphorylating SARS-CoV-2 protein N |
N-M (5) and M-AKT (6) kinase |
(5) Li et al. [20] (6) Laurent et al. [24] |
A549-ACE2 5 μM |
N/A |
(1) Interaction detected also in the SARS-CoV-1 interactome [18,21] (2) Retrospective real-world clinical data analysis; a reduced requirement to mechanical ventilation was observed in COVID-19 patients taking antipsychotics drugs targeting Sigma1 in comparison to COVID-19 patients taking antipsychotics drugs not targeting Sigma1 [18]. (3) Conserved interaction detected also in the SARS-CoV-1 and in the MERS-CoV interactome [18]. (4) Non-interventional study; reduced hospitalization of COVID-19 patients users of indomethacin targeting PGES-2 in comparison to COVID-19 patients users of anti-inflammatory drug Celecoxib not targeting PGES-2 which does not have anti–SARS-CoV-2 activity in vitro [18]. (5) An N-M intraviral PPI interaction was detected by Li et al. [20] and (6) an M-AKT2 interaction was detected by Laurent et al. [24].