Table 2.

Targeting viral replication

Targets (for inhibition)	Drugs	FDA approved	Cmax (μM)	Primary indications	Virus	IC50/EC50 (μM)	Model system	CC50 (μM)	Refs
eIF2α phosphorylation	INDO GGA	Yes Yes	14.36a 0.75b	Inflammation Ulcer	Canine-CoV SARS-CoV Canine-CoV IFV-A	5 50 – –	A72 Vero Dog Mice	>550 >400 – –	68, 69, 70, 71 68, 69, 70, 71 68, 69, 70, 71 75, 76, 77
eIF4A	Silvestrol	No	1.57c	Cancers	MERS-CoV HCoV-229E	0.001 0.003	MRC-5 MRC-5	>10 >10	79, 80, 81, 82 79, 80, 81, 82
B-Raf (V600E)	Vemurafenib	Yes	126d	Orbital Erdheim- Chester disease	IFV-A	0.22–3.8e	A549	>25	88, 89, 90
MEK1/2	Trametinib	Yes	0.042f	Cancers	IFV-A IFV-A	0.016 –	A549 Mice	>20 –	85, 95, 96, 97
CDK1/2/5/9	Dinaciclib	No	–	Cancers	IFV-A	0.02–0.21g	A549	>100	[5]
CDK1/2/4/6	Flavopiridol	No	–	Cancers	IFV-A	0.24–0.7g	A549	>100	[5]

Abbreviations: C_max, the maximum serum concentration; IC₅₀/EC₅₀, the half-maximal inhibitory concentration/the half-maximal effective concentration; CC₅₀, the half-maximal cytotoxic concentration.

^aThe dosage for moderate-to-severe rheumatoid arthritis in patient is 25 mg two or three times a day (FDA Guidance). Oral administration to dogs results in the C_max of 14.36 μM by 1.4 h [69].

^bOral administration of 50 mg results in the mean C_max of 0.75 μM by 5.35 h [76].

^cIntravenous injection of 5 mg/kg to mice results in the C_max of 1.57 μM [81].

^dOral administration of 960 mg to patients twice a day results in the mean C_max of 126 μM (FDA Guidance). Treatment of mice with 100 mg/kg results in the C_max of 124 μM by 2 h [89].

^eIC₅₀ values at low micromolar concentrations against virus strains of H7N7 and H7N9 [90].

^fOral administration of 2 mg to patients reaches the peak serum concentration by 1.5 h (FDA Guidance). Oral administration of 0.1 mg/kg to mice results in the C_max of 0.042 μM by 4 h 95, 96.

^gIC₅₀ values for IFV-A strains H7N9, H1N1 and H3N2 [5].