Kinases as Potential Therapeutic Targets for Anti-coronaviral Therapy

Abstract

The global coronavirus disease-19 (COVID-19) has affected more than 140 million and killed more than 3 million people worldwide as of April 20, 2021. The novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been identified as an etiological agent for COVID-19. Several kinases have been proposed as possible mediators of multiple viral infections, including life-threatening coronaviruses like SARS-CoV-1, Middle East syndrome coronavirus (MERS-CoV), and SARS-CoV-2. Viral infections hijack abundant cell signaling pathways, resulting in drastic phosphorylation rewiring in the host and viral proteins. Some kinases play a significant role throughout the viral infection cycle (entry, replication, assembly, and egress), and several of them are involved in the virus-induced hyperinflammatory response that leads to cytokine storm, acute respiratory distress syndrome (ARDS), organ injury, and death. Here, we highlight kinases that are associated with coronavirus infections and their inhibitors with antiviral and potentially anti-inflammatory, cytokine-suppressive, or antifibrotic activity.

Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure–Activity Relationships, Antiviral Activity, and X-ray Structure Determination

“… 41 The inhibition of JAK-3 is a promising approach for the treatment of COVID-19 as it reduces the inflammatory/cytokine storm that is one of the major factors for the organ damage that leads to death. 42 Indeed, many JAK inhibitors are already in advanced clinical trials for the treatment of COVID-19. 43 Therefore, inhibitors targeting the viral main protease and JAK would not only have direct antiviral effects but also beneficially suppress the overproduction of cytokines induced by viral infection.…”

Charting the Unknown Association of COVID-19 with Thyroid Cancer, Focusing on Differentiated Thyroid Cancer: A Call for Caution

“…Second, whether L-T4 binding to integrin αvβ3 can diminish the integrin αvβ3-mediated internalization of the SARS-CoV-2 is yet to be investigated. Third, as kinases are involved in the virus-induced cytokine storm, tyrosine kinases inhibitors (TKI)—used for treatment of advanced (D)TC—are under evaluation as antiviral agents against SARS-CoV-2 [ 124 , 125 ]. Fourth, L-T4 titration after (D)TC surgery in patients with COVID-19 may be hampered by TSH suppression due to non-thyroidal illness syndrome (NTIS) caused by COVID-19, or due to exogenous corticosteroids used for treatment of severe COVID-19 [ 126 ].…”

Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of COVID-19

“… Schematic representation of SARS-CoV-2 life cycle at different stages and possible inhibitors acting on specific target ( Pillaiyar and Laufer, 2021 ). …”

“…Silmitasertib exhibited significant antiviral activity with an IC 50 of 1.28 M, suggesting that it may have a prominent role in the SARS-CoV-2 life cycle. A phase II clinical trial is under way on the use of silmitasertib in COVID-19 management ( Pillaiyar and Laufer, 2021 ).…”