TABLE 2.
Potential alternative approaches to treat macrophage-induced complications in COVID-19 patients.
| Target | Drug | Mechanism | Ref |
|---|---|---|---|
| Increase interferon signaling | |||
| TLR7 | Imiquimod | Increase in IFN-α, IFN-β, and IFN-γ | (Megyeri et al., 1995; Wang et al., 2005; Huang et al., 2009; O’Brien et al., 2010) |
| TLR9 | CpG oligodeoxy-nucleotides | Increase IFN-α expression and infiltration of CD4 T cells and | (Wang et al., 2005) |
| TLR3 | poly (I:C) | Stimulate RLR pathway through RIG-I to upregulate IFN-β | (Dauletbaev et al., 2015) |
| dsRNA sensors | DNA methyltransferase inhibitors | Demethylation of endogenous retroviruses triggers dsRNA response, thus increasing IFN-β | (Chiappinelli et al., 2015) |
| Decrease macrophage recruitment | |||
| CCL2 | Bindarit | Decrease CCL2 expression, decrease monocyte/macrophage infiltration | (Baeck et al., 2012; Ge et al., 2012, 2; Mora et al., 2012) |
| CCL5 | Met-RANTES | Reduce inflammatory cell recruitment and cytokine production | (Culley et al., 2006) |
| CX3CL1/CX3CR1 | AZD8797 | Decrease inflammation and macrophage activation | (Karlström et al., 2013, 3; Wollberg et al., 2014) |
| M2-like macrophages | Nexturastat A | Decreases M2-like macrophage recruitment | (Knox et al., 2019; Banik et al., 2020) |
| Decrease cytokine storm | |||
| Expression of pro-inflammatory cytokines like IL-6, IL-1β, and TNF-α | Trichostatin A | Decreases IL-6 production by modulating mRNA stability | (Grabiec et al., 2011) |
| Decrease IL-1β, and TNF-α | (Han and Lee, 2009) | ||
| Decrease systemic inflammation | (Cui et al., 2019) | ||
| CKD-L | Decrease TNF-α and IL-1β | (Oh et al., 2017) | |
| Tubastatin A | Decrease IL-6 and TNF-α, improves survival, and decreases liver injury | (Li et al., 2015) | |
| Vorinostat | Reduce cytokine storm induced by administration of anti-CD3 antibodies | (Li et al., 2008) | |
| STAT signaling | Tubastatin A | Decrease STAT3 phosphorylation | (Cheng et al., 2011, 2014) |
| Decrease pulmonary fibrosis | |||
| Fibroblast viability; expression of fibrogenesis-associated genes | Panobinostat | Decrease gene expression of fibrogenesis-associated genes; induce cell cycle arrest and apoptosis in fibrocytes | (Korfei et al., 2014, 2018) |
| Tubastatin A | Decrease TGF-β-induced expression of type I collagen in lung fibroblast | (Saito et al., 2017) | |
| SAHA | Induce apoptosis in myofibroblasts, decrease pulmonary fibrosis, and increase lung function | (Sanders et al., 2014) | |
TLR, Toll-like receptor; IFN-α/β/γ, interferon alpha/beta/gamma; RLR, RIG-I-like receptor; dsRNA, double stranded RNA; CCL2/CCL5, C-C motif chemokine ligand 2/5; CX3CL1/CX3CR1, C-X3-C motif chemokine ligand/receptor 1; IL-6, interleukin 6; IL-1β, interleukin 1 beta; TNF-α, tumor necrosis factor alpha; STAT, signal transducer and activator of transcription; TGF-β, transforming growth factor beta; SAHA (suberoylanilide hydroxamic acid.