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Review
. 2022 Jan 27;65(2):935-954.
doi: 10.1021/acs.jmedchem.1c00302. Epub 2021 May 10.

Kinase Inhibitors as Underexplored Antiviral Agents

Javier García-Cárceles  1 , Elena Caballero  1 , Carmen Gil  1 , Ana Martínez  1
Affiliations
Review

Kinase Inhibitors as Underexplored Antiviral Agents

Javier García-Cárceles et al. J Med Chem. .

Abstract

Viral infections are a major health problem; therefore, there is an urgent need for novel therapeutic strategies. Antivirals used to target proteins encoded by the viral genome usually enhance drug resistance generated by the virus. A potential solution may be drugs acting at host-based targets since viruses are dependent on numerous cellular proteins and phosphorylation events that are crucial during their life cycle. Repurposing existing kinase inhibitors as antiviral agents would help in the cost and effectiveness of the process, but this strategy usually does not provide much improvement, and specific medicinal chemistry programs are needed in the field. Anyway, extensive use of FDA-approved kinase inhibitors has been quite useful in deciphering the role of host kinases in viral infection. The present perspective aims to review the state of the art of kinase inhibitors that target viral infections in different development stages.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Representative chemical structures of FDA-approved PKIs for cancer or inflammatory processes and antitumoral LKIs with antiviral properties in clinical trials.
Figure 2
Figure 2
Chemical structures of GAK, AAK1, and BIKE inhibitors with antiviral activity.
Figure 3
Figure 3
Chemical structures of 3,6-disubstituted isothiazolo[4,3-b]pyridines 21–27 with antiviral activity.
Figure 4
Figure 4
Chemical structures of imidazo[1,2-b]pyridazines 28 and 29, and pyrrolo[2,3-b]pyridines 30 and 31 with antiviral activity.
Figure 5
Figure 5
Chemical structures for GAK and AAK1 probes 32 and 33, and their structurally related negative controls 34 and 35, respectively.
Figure 6
Figure 6
Chemical structures of representative RTK inhibitors with antiviral activity.
Figure 7
Figure 7
MAPK signaling cascade upon binding of a GF to its receptor, leading to the activation of MAPKAPK.
Figure 8
Figure 8
Chemical structures of representative MAPK inhibitors with antiviral activities.
Figure 9
Figure 9
Chemical structures of FDA-approved Src kinase inhibitors with antiviral activity.
Figure 10
Figure 10
Chemical structures of the first molecules identified as CDK inhibitors with antiviral activities.
Figure 11
Figure 11
Chemical structures of representative PIKfyve inhibitors bearing a morpholino-azine core group.
Figure 12
Figure 12
Chemical structures of inhibitors 1, 5, 17, 19, and 56–61 with antiviral activity.
See this image and copyright information in PMC

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