Table 2.

Nonclinical studies focused on immunotherapy with potential benefits to COVID-19 treatment.

Product	Potential benefits for COVID-19	Reference
Daclatasvir	Antiviral compounds with immunomodulatory effect: reduce viral load and proinflammatory cytokines using in vitro cell cultivation with SARS-CoV-2	Sacramento et al. [160]
Bovine lactoferrin	Antiviral compounds with immunomodulatory effect: reduce viral load and possible reduction of proinflammatory cytokines and induction of T cell activation	Carvalho et al. [167]
Kepi—inhibitory subunit of the protein phosphatase 1 complex (PP1)	Inhibition/blockade of immune response pathways: reduce signaling of inflammatory cytokines, as TNF-α in mice models infected with SARS-CoV	McDermott et al. [176]
Hybrid IFN-α B/D	Inhibition/blockade of immune response pathways: it was effective to inhibit SARS-CoV replication in Vero cells by in vitro assays and could reduce SARS-CoV replication in the lungs of infected mice	Barnard et al. [177]
CCR2 antagonist/anti-CCR2	Inhibition/blockade of immune response pathways: may promote monocyte egress from the bone marrow and monocyte recruitment in tissues	Merad and Martin [140]
IRAK4 inhibitor/PF-06650833; CA-4948	Inhibition/blockade of immune response pathways: may reduce inflammation caused by macrophages, mediates TLR and IL-1β signaling	Merad and Martin [140]
PAR-1 antagonist (SCH530348), PAR-1 antagonist receptor (SCH79797)	Anticoagulants: may reduce levels of proinflammatory cytokines, neutrophilic lung inflammation, and other harmful pathological effects that are associated with the disseminated intravascular coagulation in COVID-19	Khoufache et al./Bacil et al. [179, 183]
Inhibitor of Bruton's tyrosine kinase (BTKi)	Immunotherapeutic approaches with similarities to other immunopathological diseases: may reduce B cell responses and macrophage polarization, as observed in patients with B cell malignancies	Chong et al. [180]