*4.8. Alternative Drugs to Inhibit the Cytokine Storm Syndrome*

Among alternative drugs that may have the ability to inhibit the systemic hyperinflammation in COVID-19 are IL-6 blockers (Tocilizumab, Sarilumab), IL-1 blocker (Anakinra, Canakinumab), heparins (low molecular weight and unfractionated heparin), intravenous immunoglobulins (IVIG), hyperimmune immunoglobulins (neutralizing antibodies), JAK inhibitors (Ruloxitinib, Bariticinib), corticosteroids (methylprednisolone, dexamethasone), statins and recombinant human angiotensin-converting enzyme 2 (rh ACE2). These are discussed elsewhere [61].

Interestingly, there is another CypA inhibiting drug, without immunosuppressive activity, named alisporivir [16,62,63]. It is a non-immunosuppressive analogue of CsA with strong Cyps inhibition properties. Alisporivir has reached phase three clinical development for the treatment of COVID-19 [63].

Preclinical data show strong antiviral and cytoprotective properties of alisporivir in various models of coronavirus infection, including SARS-CoV-1, MERS-CoV and SARS-CoV-2 [63]. Nevertheless, an important question remains if alisporivir can also inhibit the cytokine storm syndrome, as it has no immunosuppression activity.
