Table 1.

Inhibitors targeting Coronaviruses found in the literature.

Structure	Source	Organism	IC50	Target	PDB - Interactions/(H-bond)	Ref.
Spike (S) protein
EEQAKTFLDKFNHEAEDLFYQSSGLGKGDFR	Synthetic	SARS-CoV	0.1 µM	S protein	Not revealeda	209
Chymotrypsin-like cysteine protease (3CLpro)
	Synthetic	SARS-CoV	57 µM	3CLpro	(PDB: 4TWW) - Cys145, His41, Met49, Met165, Asp187, His163(H), Phe140, Leu141, and Glu166	210
	Synthetic	SARS-CoV	30 µM	3CLpro	(PDB: 3AW1) - Cys145(H) and Gln189(H)	211
	Synthetic	SARS-CoV	5.8 µM	3CLpro	(PDB: 2ALV) - Gly143(H), Ser144(H), Cys145(H), His163(H), His41(H), Leu27, Met49, and Gln189	212
	Synthetic	HCoV-NL63	1.08 µM	3CLpro	(PDB: 6FV2) - His41(H), *Gly142(H), Phe139(H), and Glu166(H).	213
	Synthetic	SARS-CoV	0.24 µM	3CLpro	(PDB: 5N5O) - Met49, Met165, Asp187, Gln189(H), and Thr190	213
	Synthetic	MERS-CoV	1.7 µM	3CLpro	(PDB: 4RSP) - Glu166(H), Glu169(H), Gln192(H), Cys148 (Covalent), and His41	214
		SARS-CoV	0.2 µM	3CLpro	Not revealeda	214
	Synthetic	SARS-CoV	0.51 µM	3CLpro	(PDB: 2AMD) - Phe140, Leu141, His163, Met165, Glu166, His172, Asn142(H), Gly143(H), and Cys145(H)	215
	Synthetic	MERS-CoV	0.4 µM	3CLpro	(PDB: 5WKL) - Cys148, Gln192(H), *Gln167(H), Glu169(H), His41(H), *His166(H), and *Phe143(H)	216
		SARS-CoV	5.1 µM	3CLpro	Not revealeda	216
	Synthetic	MERS-CoV	0.6 µM	3CLpro	Not revealeda	216
		SARS-CoV	2.1 µM	3CLpro	Not revealeda	216
	Synthetic	SARS-CoV	26 µM	3CLpro	(PDB: 4TWW) - Cys145, His163(H), Phe140, Leu141, and Glu166	217
	Synthetic	SARS-CoV	95 µM	3CLpro	Not revealeda	218
	Synthetic	MERS-CoV	0.28 µM	3CLpro	(PDB: 1UK3) - Cys148 (Covalent), *His166(H), and His175(H)	219, 220
	Synthetic	SARS-CoV	4.6 µM	3CLpro	(PDB: 3VB5) - Cys145(Covalent), Pro168, Thr190(H), Glu166(H), Gln189(H), His164(H), Phe140(H), and His163(H)	221
	Synthetic	SARS-CoV	0.23 µM	3CLpro	Not revealeda	222
	Synthetic	SARS-CoV	6.1 µM	3CLpro	(PDB: 1UK4) - Glu166(H), Gly143(H), Cys145(H), Met49, and Gln189	223
	Synthetic	SARS-CoV	24.1 µM	3CLpro	Not revealeda	224
	Natural	SARS-CoV	8.3 µM	3CLpro	(PDB: 2Z3E) - Leu141(H), His163(H), Val186(H), Gln189(H), and Gln192(H),	225
	Natural	SARS-CoV	8.3 µM	3CLpro	Not revealeda	226
	Synthetic	SARS-CoV	1.0 µM	3CLpro	Not revealeda	227
	Synthetic	SARS-CoV	10.0 µM	3CLpro	(PDB: 1UK4) - His41, Met49, Phe140, Gly143(H), Cys145(H), His163, Met165, Glu166(H), Pro168, and Gln189(H)	228
	Synthetic	SARS-CoV	1.7 µM	3CLpro	Not revealeda	229
	Synthetic	SARS-CoV	10.0 µM	3CLpro	(PDB: 1WOF) - Cys145, Ser144(H), His163(H), His164(H), Glu166(H), and Gln189(H)	230
	Synthetic	SARS-CoV	0.74 µM	3CLpro	(PDB: 1WOF) - Cys145, Ser144(H), His163(H), His164(H), Glu166(H), and Gln189(H)	231
	Synthetic	SARS-CoV	5.0 µM	3CLpro	(PDB: 1UK4) - Glu166(H), His163(H), Cys145(H), Ser144(H), Asn142(H), Phe140(H), Thr26(H), and His41	232
	Synthetic	SARS-CoV	0.5 µM	3CLpro	Not revealeda	233
	Synthetic	SARS-CoV	3.0 µM	3CLpro	Not revealeda	234
	Natural	SARS-CoV	10.0 µM	3CLpro	Not revealeda	235
	Synthetic	SARS-CoV	13.0 µM	3CLpro	Not revealeda	236
	Synthetic	SARS-CoV	8.9 µM	3CLpro	Not revealeda	237
		SARS-CoV	2.5 µM	3CLpro	Not revealeda	238
	Synthetic	SARS-CoV	17.2 µM	3CLpro	Not revealeda	239
	Synthetic	SARS-CoV	1.5 µM	3CLpro	Not revealeda	240
	Natural	SARS-CoV	2.7 µM	3CLpro	(PDB: 2ZU5) - Thr190(H), His163(H), Ser144(H), His41(H), and Cys145(H)	241
	Synthetic	SARS-CoV	13.9 µM	3CLpro	Not revealeda	242
	Synthetic	SARS-CoV	1.04 µM	3CLpro	(PDB: 1UK4) - Met49, Leu141, Asn142, Gly143(H), Ser144, Cys145(H), Met165, Arg188, Gln189, and Gln192	243
	Synthetic	SARS-CoV	0.95 µM	3CLpro	(PDB: 1UK4) - Gly143(H), Cys145(H), His41(H), His164, Phe140, His163, and Met165	244
	Synthetic	SARS-CoV	0.3 µM	3CLpro	(PDB: 1UK4) - Met49, His41(H), Pro39, Leu27, Cys145, His164, Met165, Leu167, Gln192, and Gln189	245
	Synthetic	SARS-CoV	0.06 µM	3CLpro	(PDB: 2A5A) - Glu189, Met49, His41, Cys145, Gly143(H), His163(H), Phe140, His172, and Glu166	246
	Synthetic	SARS-CoV	0.051 µM	3CLpro	Not revealeda	247
	Synthetic	SARS-CoV	0.098 µM	3CLpro	(PDB: 3ATW) - Thr90(H), Glu166(H), His163(H), Phe140, Leu141, Asn142, His41, Met49, Met165, Asp187, and Cys145(H).	248
	Natural	SARS-CoV	27.5 µM	3CLpro	(PDB: 4WY3) - Gln166(H), Leu167(H), Phe140(H), Gln189(H), Asn142(H), Thr26(H), and Thr24(H).	249
	Natural	SARS-CoV	11.4 µM	3CLpro	(PDB: 2ZU5) - His163(H), Ser144(H), and Cys145(H)	250
	Synthetic	MERS-CoV	5.8 µM	3CLpro	(PDB: 4YLU) - His41, Ser147, Glu169(H), Leu170, Val193, and Gln195	212
	Synthetic	SARS-CoV2	0.67 µM	3CLpro	(PDB: 6Y2F) - His41(H), Gly143(H), Cys145(H), Ser144(H), Phe140(H), Glu166(H), and His163(H)	127
		SARS-CoV	0.90 µM	3CLpro	Not revealeda	127
		MERS-CoV	0.58 µM	3CLpro	Not revealeda	127
	Synthetic	SARS-CoV	9.6 µM	3CLpro	(PDB: 1UK4) - Glu166(H), Gly143, Gln192, Met49, Arg188, and Gln189	251
Papain-like protease (PLpro)
	Synthetic	SARS-CoV	(a) 0.46 µM and (b) 1.3 µM	PLpro	(PDB: 3E9S) - Tyr269, Gln270, and Asp165	252
	Synthetic	SARS-CoV	14.2 µM	PLpro	(PDB: 4M0W) - Cys271	253
		MERS-CoV	22.7 µM	PLpro	Not revealeda	253
		SARS-CoV	5.0 µM	PLpro	Not revealeda	254
	Synthetic	MERS-CoV	6.6 µM	PLpro	(PDB: 4RF1) - Tyr279(H), Ser167(H), Pro163, Asp164, Asp165, *Gly248, *Thr249, Pro250, *Phe269, Glu273, Ala275, Val276, Gly277, and Thr308	255
	Natural	SARS-CoV	0.8 µM	PLpro	Not revealeda	256
	Natural	SARS-CoV	5.0 µM	PLpro	Not revealeda	257
	Synthetic	SARS-CoV	(a) 0.39 µM and (b) 0.35 µM	PLpro	(PDB: 3 MJ5) - Cys112, *Leu163, Asp165, Pro248, Pro249, Tyr265, Tyr269, Gln270, Tyr274, Thr302, and Asp303	258
	Natural	SARS-CoV	1.2 µM	PLpro	(PDB: 3 MJ5) - His176(H) and His172(H)	250
	Synthetic	SARS-CoV	8.45 µM	PLpro	(PDB: 2FE8) - His290, Asp287, His273, Ala289, Lys106(H), Cys112(Covalent), and Trp107(H).	259b
		SARS-CoV2	2.26 µM	PLpro	(PDB: 6W9C) - *Leu289, Ala288, Asp286, Lys105, Tyr268, *Trp106, His272, and *Cys111(Covalent).	259b
NTPase/Helicase (nsP13)
	Synthetic	SARS-CoV	6 µM	nsP13	Not revealeda	260
			12 µM 50 µM 5.9 µM	Y277AnsP13 K508AnsP13 WTnsP13	(homology model) Tyr277, Arg507, and Lys508.	261
	Synthetic	MERS-CoV	2.5 µM	nsP13	(homology model) Tyr7, Tyr159, Arg163, and Tyr171.	261, 262
([Bi(L5) (H2O) (ClO4)3], L5 =	Synthetic	SARS-CoV	5.0 µM	nsP13	Not revealeda	263
	Synthetic	SARS-CoV	3.0 µM	nsP13	Not revealeda	264
	Synthetic	SARS-CoV	11.0 µM	nsP13	Not revealeda	265
Guanine-N7-Methyltransferase (also named as N7-MTase or nsP14)
	Synthetic	SARS-CoV	0.6 µM	nsP14	(PDB: 5C8T) - Trp385, Phe401, Tyr420, Phe426, Phe506, Cys387, Pro335, Val290, Trp292, Ile332, Phe367, Ala353, Val389, Asn386 (H), Arg310 (H), Gly333 (H), Ile338 (H), Lys336 (H), His424 (H), and Asp352 (H).	266

*: Divergent residue labeling due to the difference between the SARS-CoV, SARS-CoV-2, and MERS-CoV proteins’ structures. ^a: The authors have not performed in silico studies. ^b: Preprint study published online at BioRxiv, doi: 10.1101/2020.05.17.100768, available at: https://www.biorxiv.org/content/10.1101/2020.05.17.100768v1.