Table 1.
Potential antiviral efficacy of DMARDs and immunosuppressants for SARS-CoV-2.
| Medications | Proposed antiviral mechanisms | In vitro | Clinical report |
|---|---|---|---|
|
Chloroquine
HCQ |
(1) Increase endosomal pH required for virus/cell fusion (2) Interfere with the glycosylation of cellular receptors |
✓ | ✓ Cohort (n = 42): negative RT-PCR rate on day 6 HCQ group: 70% (13/20) Control group: 12.5% (2/16) HCQ + azithromycin group: 100% (6/6)7 ✗ RCT (n = 30): no significant difference8 ✓ Open label, no control group (n = 80): with azithromycin, 65/80 improved clinical outcomes9 ✓ RCT (n = 62): significant improvement in time to clinical recovery and radiologic change (p < 0.05)10 ✓ RCT (n = 22): shorten hospital days and greater radiologic improvement, but not significant compared to control (Lopinavir/Ritonavir)11 ✗ RCT (n = 150): only significant in CRP reduction (p = 0.045)12 |
| Baricitinib | (1) Regulate endocytosis of virus by inhibiting AAK1, GAK. (2) Reduce cytokines including IL-2, IL-6, IL-10, G-CSF, and IFN-γ |
✓ n = 4, improved clinically and in laboratory data.13
✓ Placebo-controlled, open-label study (n = 24): significant improvement in baricitinib group14 |
|
| Cyclosporine A | (1) Target cyclophilin D to inhibit MPTP opening and rescues mitochondria from apoptosis. (2) MDA5, a putative cytoplasmic receptor of SARS-CoV-2, could be reversed by calcineurin inhibitors |
||
|
MMF
MPA |
Inhibit DHODH and IMPDH | ✓ | |
| Thalidomide | Suppress pro-inflammatory cytokines (TNF-α, IL-8) through inhibition of NF-κB | ✓ n = 1: 45 years, woman15 |
AAK1, AP2-associated protein kinase 1; CRP, C-reactive protein; DHODH, dihydroorotate dehydrogenase; GAK, cyclin G-associated kinase; G-CSF, granulocyte-colony-stimulating factor; IL, interleukin; HCQ, hydroxychloroquine; IFN, interferon; IMPDH, inosine monophosphate dehydrogenase; MDA5, melanoma-differentiation-activated protein 5; MMF/MPA, mycophenolate mofetil/mycophenolic acid; MPTP, mitochondrial permeability transition pore opening; RCT, randomized-controlled trial; RT-PCR, real-time polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor.