Table 2.

Inhibitors of various enzymes involved in RNA capping and the various assays used for their screening.

Inhibitor[a]	Method (activity)	Enzyme (organism)	IC50 [μM]
ATPγS	Radioactive assay (TPase)	NS3 (DENV)	∼500 [71]
Pyrophosphate	Radioactive assay (NTPase)	cvRtp1 (Chlorella virus)	2.4 [77]
Tripolyphosphate	Radioactive assay (NTPase)	cvRtp1 (Chlorella virus)	0.6 [77]
Irigenol	Transcreener™ ADP assay (NTPase)	TbCet1 (Trypanosoma brucei)	0.065 [81]
2′,2′‐Bisepigallocatechin monogallate	Transcreener™ ADP assay (NTPase)	TbCet1 (Trypanosoma brucei)	0.010 [81]
Suramin	Charcoal adsorption assay (TPase) Py‐FLINT (N7‐MTase) Py‐FLINT (N7‐MTase) Py‐FLINT (N7‐MTase)	Cet1p (Saccharomyces cerevisae) VCE (Vaccinia virus) Ecm1 (E. cuniculi) RNMT‐RAM (Homo sapiens)	1.9±0.3 [74] 0.083±0.015 [133] 0.046±0.006 [133] 0.70±0.08 [133]
Ellagic acid	Transcreener™ ADP assay (NTPase) HRTF (N7‐MTase)	TbCet1 (Trypanosoma brucei) nsp14 (SARS‐CoV)	0.035 [81] 0.16±0.02 [115]
Chembridge3 5660163	FP (GTase)	NS5 (DENV)	7.1±1.4 [103]
Maybridge5 GK 02514	FP (GTase)	NS5 (DENV)	9.8±1.0 [103]
Chembridge3 7871678	FP (GTase)	NS5 (DENV)	7.4±0.8 [103]
Benzbromarone	FP (GTase)	NS5 (DENV) nsP1 (CHIKV)	9±0.7 [104] 13.0±0.9 [104]
Pyrantel pamoate	FP (GTase)	NS5 (DENV) nsP1 (CHIKV)	38±1.5 [104] 5.0±0.3 [104]
Pyrimethamine	Western blot assay (GTase) Filter binding assay (N7‐MTase)	nsP1 (VEEV)	2.7±0.4 [106] 73.5±2.9 [106]
(3‐Fluorobenzyl)‐N6‐SAH	SPA (N7‐MTase) SPA (2′‐O‐MTase)	NS5 (DENV)	0.77±0.04 [122] 0.19±0.03 [122]
(3‐Chlorobenzyl)‐N6‐SAH	SPA (N7‐MTase) SPA (2′‐O‐MTase)	NS5 (DENV)	0.82±0.06 [122] 0.17±0.02 [122]
(3‐Methylbenzyl)‐N6‐SAH	SPA (N7‐MTase) SPA (2′‐O‐MTase)	NS5 (DENV)	0.85±0.04 [122] 0.28±0.03 [122]
NF 023	Py‐FLINT (N7‐MTase)	Ecm1 (E. cuniculi)	0.015±0.005 [133]
Aurintricarboxylic acid	Py‐FLINT (N7‐MTase)	Ecm1 (E. cuniculi)	0.031±0.005 [133]
Reactive Blue 2	Py‐FLINT (N7‐MTase)	nsp14 (SARS‐CoV‐2) Ecm1 (E. cuniculi)	4.12±0.74 [134] 0.043±0.007 [133]
Myricetin	Py‐FLINT (N7‐MTase) HRTF (N7‐MTase) Py‐FLINT (N7‐MTase)	nsp14 (SARS‐CoV‐2) nsp14 (SARS‐CoV) Ecm1 (E. cuniculi)	6.18±0.54 [134] 2.0±0.6 [115] 0.14±0.01 [133]
Quercetin	Py‐FLINT (N7‐MTase) HRTF (N7‐MTase) Py‐FLINT (N7‐MTase)	nsp14 (SARS‐CoV‐2) nsp14 (SARS‐CoV) Ecm1 (E. cuniculi)	11.2±1.4 [134] 3.3±0.7 [115] 0.12±0.02 [133]
SCH 202676 HBr	Py‐FLINT (N7‐MTase)	nsp14 (SARS‐CoV‐2)	1.50±0.20 [134]
Thimerosal	Py‐FLINT (N7‐MTase)	nsp14 (SARS‐CoV‐2)	1.05±0.08 [134]
Nitazoxanide	RapidFire MS (N7‐MTase)	nsp14 (SARS‐CoV‐2)	9.7 [131]
Adenosine dinucleotide SAM analogue	Filter binding assay (N7‐MTase)	nsp14 (SARS‐CoV)	0.6±0.1 [145]
2‐Hydroxy‐4‐oxo‐4‐phenyl‐2‐butenoic acid	Radioactive assay (endonuclease)	PA endonuclease (influenza virus)	65.0 [137]
Diketo acid analogue	TSA (endonuclease)	PA endonuclease (Andes virus)	3.4±0.5 [142]
Baloxavir acid (BXA)	TSA and Urea PAGE with fluorescence visualization (endonuclease)	PA endonuclease (influenza virus)	n.d. [138]
P‐30	FRET assay (endonuclease)	PA endonuclease (influenza virus)	1.5±0.2 [67]
ANA‐0	FRET assay (endonuclease)	PA endonuclease (influenza virus)	0.8±0.1 [67]