Table 1.

Viral applications.

DARPin Name	Target/Epitope	Mechanism of Action	Application	Ref.
1D3 2E6	Ad5 knob Her2	Bispecific adapter to retarget Ad5 to tumor cells	Tumor retargeting of Ad5	[51,58]
9.26 9.01 9.16 G3 9.29 H14R	Her2	Engineered MeV attachment protein Hemagglutinin unable to bind to its natural receptor genetically fused to a Her2-specific DARPin binding domain	Tumor retargeting of pseudotyped lentiviral vector	[61]
D29.2	CD4	Engineered MeV attachment protein Hemagglutinin unable to bind to its natural receptor genetically fused to a CD4-specific DARPin binding domain	Retargeting pseudotyped lentiviral vector to CD4+ cells	[62]
9.16 9.29 9.26 G3	Her2	Engineered MeV attachment protein Hemagglutinin unable to bind to its natural receptor genetically fused to either Her2, EpCAM or EGFR-specific DARPin bindingdomain (Monospecific or bispecific G3 +EC4)	Tumor retargeting of recombinant MeV	[59]
C9 EC4	EpCAM
E.01 E.68 E.69	EGFR
E.01	EGFR	Engineered MeV fusion protein (F) that can be activated by tumor-associated matrix metalloprotease, genetically fused to EGFR-specific DARPin binding domain	Tumor retargeting of recombinant MeV	[60]
9.29	Her2	Engineered capsid protein VP2 fused to Her2-specific DARPin binding domain and ablated natural receptor binding site on VP3	Tumor retargeting of AAV	[63,64]
EC1	EpCAM	Engineered capsid protein VP2 fused to EpCAM-specific DARPin binding domain and ablated natural receptor binding site on VP3	Tumor retargeting of AAV	[64]
D55.2	CD4	Engineered capsid protein VP2 fused to CD4-specific DARPin binding domain and ablated natural receptor binding site on VP3	Retargeting AAV to CD4+ cells	[64]
E.01	EGFR	Engineered capsid protein VP2 fused to human FK-binding protein (FKBP) and ablated natural receptor binding site on VP3. Adapter protein that consist of a modified FKBP rapamycin binding domain of mTOR fused to mCherry and EGFP-specific DARPin binding domain	Adaptor for the tumor retargeting of AAV	[74]
E.01	EGFR	Engineered capsid protein VP2 fused to EGFR-specific DARPin binding domain and ablated natural receptor binding site on VP3	Tumor retargeting of AAV	[75]
F10	Human HDAC6 zinc finger domain	Impairs interaction with ubiquitin and infection by influenza and Zika virus	antiviral	[65]
AnkGAG1D4	HIV-1 Gag precursor	Interferes with late stages of HIV-1 capsid assembly	antiviral	[34,66,67,68,69]
D1.1-D6.1 D23.2 D25.2 D27.2 D29.2 D55.2 D57.2	CD4	Inhibit HIV-1 cell entry by blocking the binding to CD4, the main receptor of HIV-1	antiviral	[70]
D_18 D_19 D_20	Lactococcal phage TP901-1 BppU BppL complex	Neutralization of phage TP901-1 by blocking receptor binding	antiviral	[71]
bnD_1 bnD_2 bnD_3	V3 crown of the HIV-1 envelope protein (gp120)	Neutralization of HIV-1 by blocking receptor binding	antiviral	[73]
5m3_D12	V3 loop of the HIV-1 envelope protein (gp120)	Neutralization of HIV-1 by blocking receptor binding	antiviral	[72]
R1 R2 R3	RBD domain of SARS-CoV-2 spike	Neutralization of SARS-CoV-2 by blocking receptor binding	antiviral Therapeutic treatment of COVID-19	[39]

Abbreviations: AAV, Adeno associated virus; Ad5, Adenovirus serotype 5; COVID-19, corona virus disease 2019; DARPin, designed ankyrin repeat protein; EGFR, epidermal growth factor receptor; EpCAM, Epithelial cell adhesion molecule; HIV-1, human immunodeficiency virus type 1; MeV, measles virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus type 2.