Data on the Docking of Phytoconstituents of Betel Plant and Matcha Green Tea on SARS-CoV-2.

Betel (Piper betle L.) and green tea (Camellia sinensis (L) O. Kuntze) have been used for a long time as traditional medicine. The docking of phytoconstituents contained in betel plant was evaluated against Mpro, and matcha green tea was evaluated against five target receptors of SARS-CoV-2 as follows: spike ectodomain structure (open state), receptor-binding domain (RDB), main protease (Mpro), RNA-dependent RNA polymerase (RdRp), dan papain-like protease (PLpro). The evaluation was carried out based on the value of binding-free energy and the types of interactions of the amino acids at the receptors that interact with the ligands.

Specifications Table

Value of the Data

The data provide information on the results of GC–MS analysis of various phytoconstituents contained in betel plant (leaf and fruit parts).

The data provide information on the interactions of various betel leaf and fruit as well as matcha green tea phytoconstituents on important enzyme and proteins of SARS-CoV-2, i.e.: spike ectodomain structure (open state) (PDB code: 6VYB), receptor-binding domain (RDB) (PDB code: 6YLA), main protease (Mpro) (PDB code: 6LU7), RNA-dependent RNA polymerase (RdRp) (PDB code: 6M71), and papain-like protease (PLpro) (PDB code: 6WX4).

The data may be useful to researchers working on COVID-19 drug discovery and development;

The data provide promising phytoconstituents for betel and matcha green tea which could serve as potential clues for the development of future therapeutics for COVID-19.

Data Description

Plants are sources of phytomedicine which has the potential to be developed as antiviral agents for SARS-C0V-2, as has been reported by previous studies [1], [2]. Betel leaf and fruit contain many phytoconstituents which reveal their uses for various therapeutic purposes. The plant or its parts can be used for the treatment of various disorders in humans such as diabetes, fungal infection, microbial infection, inflammation, antihistaminic, antiulcer, and local anesthetic [3]. Matcha, which is a green tea preparation in powder form [4], is known to have many benefits, including as a source of antioxidants and having antiviral activities [5].

The data described here include the binding free energy value (kcal/mol) of the phytoconstituents contained in betel leaf and matcha green tea which serve as ligands against various targets of SARS-CoV-2. Data on phytoconstituent from betel leaf were obtained from the results of Gas chromatography-mass spectrometry (GC–MS), while information about the phytoconstituent of matcha was obtained through literature searches. The data on the drug-likeness of the ligands based on Lipinski's rule of five are listed in Table 1 for betel leaf and fruit, and Table 2 for matcha green tea. The phytoconstituents of matcha green tea were obtained from the references listed in Table 2. The data on binding free energy resulted from the docking of betel leaf and matcha green tea is presented in Tables 3 and 4, respectively. Tables 5 and 6 show the type of interaction and the interacting amino acids of the receptors with the ligands contained in betel plant and matcha green tea, respectively. The detail of interaction and visualization of the docking results of all phytoconstituents are provided in the supplementary data. The interaction visualization of the best 10 docking results of betel leaf and fruit phytoconstituents is provided in Fig. 1. The visualization of the interaction of matcha green tea with SARS-CoV-2 receptors is available from Supplementary data [6].

Table 1

Lipinski's rule of five value of betel leaf and fruit phytoconstituents.

Compound name	Molecular weight	No. H-bond acceptors	No. H-bond donors	log P	Molar refractivity	No. of violations
(5ß)Pregnane-3,20ß-diol, 14a,18a-[4-methyl-3-oxo-(1-oxa-4-azabutane-1,4-diyl)]-, diacetate	489	6	0	5.962	144.653	2
N1-Benzyl-N2(bezylidenyl-benzylamino)-	403	0	1	4.276	117.477	0
25-Norisopropyl-9,19-cyclolanostan-22-en-24-one, 3-acetoxy-24-phenyl-4,4,14-trimethyl-	516	3	0	8.118	166.353	3
Milbemycin B, 6,28-anhydro-15‑chloro-25-isopropyl-13-dehydro-5-O-demethyl-4-methyl-	590	7	1	7.752	169.584	3
1H-2,8a-Methanocyclopenta[a]cyclopropa[e]cyclodecen-11-one, 1a,2,5,5a,6,9,10,10a-octahydro-5,5a,6-trihydroxy-1,4-bis(hydroxymethyl)−1,7,9-trimethyl-, [1S-(1a,1aa,2a,5ß,5aß,6ß,8aa,9a,10aa)]-	364	6	3	3.593	100.307	0
1H-2,8a-methanocyclopenta[a]cyclopropa[e]cyclodecen-6-yl ester, [1aR-(1aa,2a,5ß,5aß,6ß,8aa,9a,10aa)]-	430	6	1	5.048	122.754	1
2,4,6-Decatrienoic acid, 1a,2,5,5a,6,9,10,10a-octahydro-5,5a-dihydroxy-4-(hydroxymethyl)−1,1,7,9-tetramethyl-11-oxo-	496	6	2	6.142	142.969	2
(2,3-Diphenylcyclopropyl)methyl phenyl sulfoxide, trans-	332	1	0	4.417	94.863	0
2-Naphthalenemethanol, decahydro-a,a,4a-trimethyl-8-methylene-, [2R-(2a,4aa,8aß)]-	240	2	2	3.833	81.209	0
benzene, 1,1′,1′'-[5-methyl-1-pentene-1,3,5-triyl]tris-	312	0	0	5.123	98.352	1

Table 2

Lipinski's rule of five value of the matcha green tea phytoconstituents.

Compound name	References	Molecular weight	No. H-bond acceptors	No. H-bond donors	log P	Molar refractivity	No. of violations
(-)-epicatechin 3,5-di-O-digallate (EC35G)	[7]	594	14	9	3.16	141.986	4
Rutin	[8]	610	16	10	−1.88	137.495	4
(-)- epigallocatechin gallate (EGCG)	[9]	458	11	8	2.23	108.921	2
Apigenin glycoside	[10]	578	12	6	1.86	144.558	4
Flavonol 3-O-d-glucoside (FOG)	[11]	400	8	4	0.45	99.615	0
Myricetin 3-glucoside (M-G)	[12]	480	13	9	−1.01	107.939	1
(-)- epigallocatechin (EGC)	[13]	306	7	6	1.25	74.288	1
Kaempferol	[14]	286	6	4	2.31	72.386	0
(-)-epicatechin gallate (ECG)	[9]	442	10	7	2.53	107.256	1
(+)-catechin	[9]	290	6	5	1.55	72.623	1
(-)-epicatechin (EC)	[9]	290	6	5	1.55	72.623	1
Myricetin	[14]	318	8	6	1.72	75.715	1
Kaempferol-3-O-glucoside	[10]	448	11	7	−0.44	104.609	2
Quercetin	[14]	302	7	5	2.01	74.050	1
(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	[15]	472	11	7	2.54	113.808	2
Caffeoylquinic acid (CQA)	[15]	354	9	6	−0.65	82.519	1
Chlorogenic acid	[8]	354	9	6	−0.65	82.519	1
Coumaric acid	[8]	164	3	2	1.49	44.776	0
Caffeic acid	[8]	180.16	4	3	1.20	46.441	0
Gallic Acid	[9]	170.12	5	4	0.50	38.395	1
Caffeine	[9]	194.19	5	0	0.06	49.100	0

Table 3

Binding free energy of betel leaf phytoconstituents against SARS-CoV-2 Mpro (6LU7).

Ligands	Chemical formula	PubChem ID	Binding affinity (kcal/mol)
(5ß)Pregnane-3,20ß-diol, 14a,18a-[4-methyl-3-oxo-(1-oxa-4-azabutane-1,4-diyl)]-, diacetate	C28H43NO6	537,242	−11.5
N1-Benzyl-N2(bezylidenyl-benzylamino)-	C28H25N3	562,008	−8.5
25-Norisopropyl-9,19-cyclolanostan-22-en-24-one, 3-acetoxy-24-phenyl-4,4,14-trimethyl-	C35H48O3	5,373,661	−8.1
Milbemycin B, 6,28-anhydro-15‑chloro-25-isopropyl-13-dehydro-5-O-demethyl-4-methyl-	C33H47ClO7	5,367,225	−8
1H-2,8a-Methanocyclopenta[a]cyclopropa[e]cyclodecen-11-one, 1a,2,5,5a,6,9,10,10a-octahydro-5,5a,6-trihydroxy-1,4-bis(hydroxymethyl)−1,7,9-trimethyl-, [1S-(1a,1aa,2a,5ß,5aß,6ß,8aa,9a,10aa)]-	C20H28O6	119,057,278	−7.9
1H-2,8a-methanocyclopenta[a]cyclopropa[e]cyclodecen-6-yl ester, [1aR-(1aa,2a,5ß,5aß,6ß,8aa,9a,10aa)]-	C24H34O6	6,918,670	−7.9
2,4,6-Decatrienoic acid, 1a,2,5,5a,6,9,10,10a-octahydro-5,5a-dihydroxy-4-(hydroxymethyl)−1,1,7,9-tetramethyl-11-oxo-	C30H40O6	5,367,323	−7.8
(2,3-Diphenylcyclopropyl)methyl phenyl sulfoxide, trans-	C22H20OS	562,543	−7.8
2-Naphthalenemethanol, decahydro-a,a,4a-trimethyl-8-methylene-, [2R-(2a,4aa,8aß)]-	C15H28O	165,258	−7.8
benzene, 1,1′,1′'-[5-methyl-1-pentene-1,3,5-triyl]tris-	C24H24	20,138,399	−7.6
3-[3-Bromophenyl]−7‑chloro-3,4-dihydro-10‑hydroxy-1,9(2H,10H)-acridinedione	C19H13BrClNO3	536,420	−7.4
(22S)−21-Acetoxy-6a,11ß-dihydroxy-16a,17a-propylmethylenedioxypregna-1,4-diene-3,20-dione	C27H36O8	544,325	−7.4
2(1H)-Pyrimidinone, 5‑chloro-4,6-diphenyl-	C16H11ClN2O	624,638	−7.3
Benz[e]azulene-3,8‑dione, 5-[(acetyloxy)methyl]−3a,4,6a,7,9,10,10a,10b-octahydro-	C19H2406	540,437	−7.3
Alpha-phenyl-alpha-tropylacetaldehyde tosylhydrazone	C22H22N2O2S	9,602,323	−7.3
Pregnan-20-one, 3-(acetyloxy)−5,6:16,17-diepoxy-, (3ß,5a,6a,16a)-	C23H32O5	265,665	−7.2
Isoaromadendrene epoxide	C15H24O	534,398	−7.1
2-[4-methyl-6-(2,6,6-trimethylcyclohex-1-enyl)hexa-1,3,5-trienyl]cyclohex-1-en-1-carboxaldehyde	C23H32O	5,363,101	−7.1
5a-Pregn-16-en-20-one, 3ß,12a-dihydroxy (22S)−6a,11ß,21-Trihydroxy-16a,17a-propyl	C25H36O5 C25H34O7	1,756,337	−7.1
Neointermedeol	C15H26O	11,877,394	−7
6-Chloro-3-(2-nitro-1-phenylethyl)−3,4-dihydro-1H-naphthalen-2-one	C18H16ClNO3	586,644	−7
Ethyl isoallocholate	C26H44O5	6,452,096	−7

Table 4

Binding free energy of matcha phytoconstituents against several SARS-CoV-2 receptors.

Ligands	PubChem CID	SARS-CoV-2 Receptors PDB ID
		6VYB	6YLA	6LU7	6M71	6WX4
		Binding free energy (kcal/mol)
(-)-epicatechin 3,5-di-O-digallate (EC35G)	467,299	−9.7	−10.0	−9.1	−9.2	−8.8
Rutin	5,280,805	−9.9	−10.1	−8.8	−8.8	−7.2
(-)-epigallocatechin gallate (EGCG)	65,064	−9.2	−9.4	−8.2	−8.5	−7.6
Apigenin glycoside	44,257,854	−9.2	−10.1	−8.7	−9.1	−7.5
Flavonol 3-O-d-glucoside (FOG)	11,953,828	−9.0	−8.1	−7.8	−7.8	−6.7
Myricetin 3-glucoside (M-G)	44,259,426	−8.8	−9.2	−8.8	−8.0	−6.6
(-)-Epigallocatechin (EGC)	72,277	−8.6	−8.4	−7.1	−7.5	−6.7
Kaempferol	5,280,863	−8.6	−7.9	−7.7	−7.1	−6.7
(-)-epicatechin gallate (ECG)	107,905	−8.5	−9.0	−8.2	−8.3	−7.4
(+)-catechin	9064	−8.4	−8.2	−7.2	−6.8	−6.6
(-)-epicatechin (EC)	72,276	−8.4	−7.8	−7.1	−7.0	−6.7
Myricetin	5,281,672	−8.4	−8.4	−7.3	−7.3	−7.1
Kaempferol-3-O-glucoside	5,282,102	−8.4	−8.9	−8.4	−7.9	−6.6
Quercetin	5,280,343	−8.3	−8.4	−7.4	−7.6	−7.0
(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	9,804,842	−8.3	−8.1	−7.6	−8.6	−7.6
Caffeoylquinic acid (CQA)	10,155,076	−8.1	−8.0	−7.2	−7.0	−6.6
Chlorogenic acid	1,794,427	−7.9	−7.3	−7.6	−6.9	−7.0
Coumaric acid	9,840,292	−6.7	−7.0	−7.2	−5.3	−6.4
Caffeic acid	689,043	−6.7	−5.9	−5.7	−5.3	−5.3
Gallic acid	370	−6.3	−6.1	−5.5	−5.6	−5.2
Caffeine	2519	−6.1	−6.0	−5.2	−5.1	−5.2

Table 5

Interacting amino acids of the main protease (6LU7) with the 10 best ligands of betel leaf and fruit.

PubChem CID	Binding free energy (kcal/mol)	No. of bonds	Interacting residues and H-bond formation
537,242	−11.5	18	Van der Waals: ASN(A142), GLY(A143) CYS(A145), HIS(A164), ASP(A187), MET(A49), TYR(A54), ARG(A188), PRO(A168), LEU(A167), THR(A190), GLN(A189), GLU(A166), MET(A165); conventional H-bond: GLN(A192); unfavorable positive-positive: HIS(A41); attractive charge and pi-anion: HIS(A41); pi-sigma: HIS(A41).
562,008	−8.5	21	Van der Waals: GLU(A166), MET(A49), THR(A24), THR(A25), THR(A26), GLY(A143), ASN(A142), ARG(A188), ASP(A187), HIS(A164), LEU(A141), GLN(A189), HIS(A163), HIS(A172), PHE(A140); unfavorable positive-positive: HIS(A41); pi-cation: HIS(A41); pi-pi t-shaped: HIS(A41); pi-alkyl: CYS(A145), LEU(A27), MET(A165).
5,373,661	−8.1	19	Van der Waals: THR(A26), THR(A25), ASN(A142), GLY(A143), HIS(A41), CYS(A145), SER(A144), LEU(A141), GLU(A166), ARG(A188), THR(A190), GLN(A192), GLN(A189), HIS(A164), MET(A49), THR(A24); conventional H-bond: THR(A45), SER(A46); pi-alkyl: MET(A165).
5,367,225	−8	14	Van der Waals: THR(A25), LEU(A27), MET(A49), GLN(A189), CYS(A145), HIS(A41), SER(A144), MET(A165), PHE(A140), LEU(A141), GLU(A166); conventional H-bond: THR(A26), GLY(A143); pi-alkyl: HIS(A163).
119,057,278	−7.9	14	Van der Waals: MET(A165), GLN(A189), ASN(A142), SER(A144), GLY(A143), HIS(A172), PHE(A140); conventional H-bond: GLU(A166), 2HIS(A163), LEU(A141); unfavorable positive-positive: 2HIS(A41); alkyl: CYS(A145)
6,918,670	−7.9	16	Van der Waals: ASN(A142), GLN(A189), HIS(A164), ASP(A187), ARG(A188), MET(A165), LEU(A141), PHE(A140), LEU(A167), PRO(A168); conventional H-bond: 3GLU(A166), HIS(A172); unfavorable positive-positive: HIS(A163); pi-alkyl: HIS(A41).
5,367,323	−7.8	13	Van der Waals: GLY(A143), HIS(A172), PHE(A140), ASN(A142), MET(A165), PRO(A168), LEU(A167); conventional H-bond: GLU(A166), HIS(A163); unfavorable positive-positive: GLN(A189); pi-alkyl: 3LEU(A141)
562,543	−7.8	15	Van der Waals: LEU(A141), PHE(A140), GLU(A166), HIS(A163), HIS(A172), HIS(A164), ASP(A187), TYR(A54), ARG(A188), GLN(A189), CYS(A145); conventional H-bond: HIS(A41); pi-cation: HIS(A41); pi-sulfur: MET(A49); pi-pi stacked & pi-alkyl: MET(A165).
165,258	−7.8	12	Van der Waals: ASP(A187), ARG(A188), GLN(A189), MET(A165), HIS(A164), MET(A49), LEU(A27), GLY(A143), ASN(A142), GLU(A166); conventional H-bond: HIS(A41); alkyl: CYS(A145
20,138,399	−7.6	15	Van der Waals: LEU(A141), PHE(A140), HIS(A172), HIS(A163), HIS(A164), ASP(A187), ARG(A188), TYR(A54), THR(A190), GLN(A189), GLU(A166); pi-sulfur: MET(A165), CYS(A145); pi-pi stacked: HIS(A41); pi-alkyl: MET(A49).

Table 6

Hydrogen bond interaction of the amino acids of the receptors with phytoconstituents in matcha. The remaining interaction data are available from Tallei et al. [6].

		Interacting amino acids
Receptors	Ligands	Conventional H-bond	Carbon H-bond	Pi-donor H-bond	Pi-carbon H-bond
6VYB	(-)-epicatechin 3,5-di-O-digallate (EC35G)	ASN(C1108), LYS(C1038)	GLY(C910), TYR(A904)
	Rutin	ARG(B1039), ARG(C1039), ARG(A1039), 2ASN(C1023), ARG(A1019)
	(-)-epigallocatechin gallate (EGCG)	2SER(B94), ASN(B99), ARG(B190)
	Apigenin glycoside	ARG(A1039), SER(B1030), THR(B1027), ASP(A1041)
	Flavonol 3-O-D-glucoside (FOG)	THR(B998), TYB(B756), THR(A998), 2ASP(A994), THR(C998)
	Myricetin 3-glucoside (M-G)	GLN(A954), GLN(A1010)	GLY(B769), 2GLN(A954)
	(-)-Epigallocatechin (EGC)	LEU(A861), LYS(A733), GLY(A1059)	PRO(A1057)
	Kaempferol	2THR(A549), ASN(B978), MET(B740), TYR(B714), ARG(B1000)	GLY(A541)
	(-)-epicatechin gallate (ECG)	GLY(C744), TYR(C741), 3ARG(31,000), LEU(C977)
	(+)-catechin	GLN(C1036), HIS(B1048)
	(-)-epicatechin (EC)	TYR(A741), MET(A740).
	Myricetin	LYS(1038), GLY(B908), HIS(B104)	TYR(B1047)
	Kaempferol-3-O-glucoside	ALA(C1020), THR(C1027), PHE(C1042), ARG(B1039;			THR(A1027)
	Quercetin	2LYS(A1038), HIS(A1048), GLY(A1048)	VAL(A1040)
	(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	2IHK(B1027), ARG(B1029)	IHK(C1027)
	Caffeoylquinic acid (CQA)	GLN(A672), ARG(A675), ARG(C1014), ARG(A1019), GLU(A773), GLN(C954)
	Chlorogenic acid	THR(A961), GLU(A1017), GLU(B773), GLN(A954)	GLY(B769)
	Coumaric acid	SER(A514), TYR(B200), PHE(A515), THR(A430)
	Caffeic acid	HIS(A1048), 2GLN(B1036)	GLY(B1035)
	Gallic acid	GLN(A1005), GLN(B1002), THR(B1006)
	Caffeine	GLU(A166), GLY(A143), SER(A144)		CYS(A142)
6YLA	(-)-epicatechin 3,5-di-O-digallate (EC35G)	TYR(L:93), LYS(H:43), ALA(H:172), 2GLU(H:152), THR(H:116), GLY(L:47)
	Rutin	GLY(H:112), THR(H:114), GLU(H:152), ALA(H:92) VAL(H:115)	GLY(L:47)
	(-)-epigallocatechin gallate (EGCG)	SER(C:62), MET(H:2), GLU(L:61), THR(H:0), THR(B:0), ASP(B:107), GLN(B:1)
	Apigenin glycoside	SER(C:174), GLN(C:172),SER(H:75);	SER(H:75), SER(C:174)
	Flavonol 3-O-d-glucoside (FOG)	2GLN(L:48)	GLN(H:39)
	Myricetin 3-glucoside (M-G)	THR(E:385), THR(H:0), ASP(H:107), SER(L:62), THR(B:0), GLN(B:1), ASP(B107)
	(-)-Epigallocatechin (EGC)	GLN(H:39)
	Kaempferol	LYS(L:45), GLN(L:44)
	(-)-epicatechin gallate (ECG)	LYS(C:213), 2ASN(C:216), 4GLU(C:219), GLY(C:218), LYS(B:218)	PRO(C:125), SER(B:132), PHE(C:122)
	(+)-catechin	GLU(H:152), GLN(L:44), LYS(L:45), GLN(H:39)
	(-)-epicatechin (EC)	LYS(L:45), GLN(L:44)
	Myricetin	ILE(H:93), GLN(H:39), GLN(L:44), LYS(L:45)		GLY(L:47)
	Kaempferol-3-O-glucoside	MET(H:2), LYS(A:386), GLN(H:3)
	Quercetin	LYS(L:45), 2GLN(L:48), ILE(H:93)
	(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	VAL(C:64), GLY(C:63), LYS(E:528), ASP(A:389). 2LYS(A:529), GLU(E:327)
	Caffeoylquinic acid (CQA)	2GLN(L:48), GLY(H:42), 2VAL(H:115), ALA(H:92)	PRO(H:41), GLN(H:39)
	Chlorogenic acid	GLY(H:28), 2ASN(H:77), ILE(H:30)
	Coumaric acid	ASP(E:389), LYS(E:386), GLY(C:63), TYR(E:369), ASN(E:370), VAL(C:64), SER(E:366), 2ASP(C:66)
	Caffeic acid	LYS(A:528), ASP(L:66), ASN(A:370)
	Gallic acid	ASN(A:388), TYR(A:369), GLU(L:61), VAL(L:64), ASP(A:364)
	Caffeine	ARG(H:59), TYR(L:31), SER(H:103)	PRO(E:412), TYR(L:98), TYR(L:31)
6LU7	(-)-epicatechin 3,5-di-O-digallate (EC35G)	THR(A24), THR(A26), THR(A46), HIS(A163), HIS(A164), MET(A165)	GLN(A189)
	Rutin	THR(A26), PHE(A140), LEU(A141), ASN(A142), GLY(A143), HIS(A163), GLU(A166), THR(A190)
	(-)-epigallocatechin gallate (EGCG)	PHE(A140), HIS(A164), MET(A165)
	Apigenin glycoside	LEU(A141), 2SER(A144), CYS(A145), HIS(A163), GLU(A166)		CYS(A145)
	Flavonol 3-O-d-glucoside (FOG)	LEU(A141), GLY(A143), SER(A144), CYS(A145)	MET(A165), GLU(A166)
	Myricetin 3-glucoside (M-G)	LEU(A141), ASN(A142), GLY(A143)
	(-)-Epigallocatechin (EGC)	HIS(A41)
	Kaempferol	TYR(A54), ASP(A187);		GLU(A166)
	(-)-epicatechin gallate (ECG)	PHE(A140), HIS(164), MET(A165)
	(+)-catechin	GLU(A166), THR(A190);	GLN(A192)
	(-)-epicatechin (EC)	THR(A26), HIS(A41), GLN(A189)
	Myricetin	GLY(A143), SER(A144), ARG(A188)		GLU(A166)
	Kaempferol-3-O-glucoside	THR(A24), THR(A26), THR(A46), HIS(A163), HIS(A164), MET(A165)	GLN(A189)
	Quercetin	TYR(A54), ASP(A187)		GLU(A166)
	(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	LEU(A141), 2CYS(A145), THR(A190), ASN(A188)	GLU(A166),
GLN(A189)
	Caffeoylquinic acid (CQA)	LEU(A141),GLY(A143), 2SER(A144), CYS(A145), HIS(A163), GLU(A166), 2THR(A190);	MET(A165)
	Chlorogenic acid	ASN(A142), SER(A144), 2THR(A190)
	Coumaric acid	LEU(A141), GLY(A143), 2SER(A144), CYS(A145), THR(A190)	PRO(A168)
	Caffeic acid	GLU(A166), GLY(A143), SER(A144)	CYS(A145).
	Gallic acid	LEU(A141), GLY(A143), CYS(A145), GLU(A166), GLN(A189)		CYS(A145)
	Caffeine	GLY(A143), GLU(A166)	LEU(A141), 2CYS(A145), GLN(A189)
6M71	(-)-epicatechin 3,5-di-O-digallate (EC35G)	THR(A:710), ASN(A:781) 2SER(A:708), LYS(A:780), SER(A:784), HIS(A:133), ASN(A:138)	LYS(A:780)
	Rutin	LYS(A:47), 2TYR(A:129), SER(A:784), LYS(A:780), ASN(A:138)	ASP(A:135)
	(-)-epigallocatechin gallate (EGCG)	3ASN(A:781), 2SER(A:709), ALA(A:706), 2SER(A:784)
	Apigenin glycoside	THR(A:394), ARG(A:349), LEU(A:245), LEU(A:251)	THR(A:319), CYS(A:395)
	Flavonol 3-O-d-glucoside (FOG)	VAL(A:675)	ARG(A:457)
	Myricetin 3-glucoside (M-G)	LYS(A:47) THR(A:710), ASN(A:781), SER(A:709)	2GLY(A:774)
	(-)-Epigallocatechin (EGC)	LYS(A:47), TYR(A:129), 2SER(A:784)
	Kaempferol	TYR(A:689), ILE(A:494), ARG(A:569), 2ASN(A:496)
	(-)-epicatechin gallate (ECG)	2SER(A:709), HIS(A:133), SER(A:784)
	(+)-catechin	TYR(A:129), SER(A:784), PHE(A:134), LYS(A:780), SER(A:772)
	(-)-epicatechin (EC)	TYR(A:129), SER(A:709), GLN(A:778), 2THR(A:710), ASP(A:711), LYS(A:47)	TYR(A:129)
	Myricetin	THR(A:710), 2SER(A:784)	GLY(A:774)
	Kaempferol-3-O-glucoside	ASN(A:781), SER(A:709), ASN(A:138)		TYR(A:129), TYR(A:32)
	Quercetin	ASN(A:628)
	(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	LYS(A:780), SER(A:784), LYS(A:47), TYR(A:32)
	Caffeoylquinic acid (CQA)	ASP(A:623), CYS(A:622), LYS(A:621), PHE(A:793), SER(A:795), ASP(A:618)
	Chlorogenic acid	THR(A:206), ASN(A:208)
	Coumaric acid	LYS(A:47), SER(A:709), 2ASN(A:781), SER(A:784)
	Caffeic acid	TYR(A:619), GLU(A:811), TRP(A:800)
	Gallic acid	ASP(A:761), TRP(A:617)
	Caffeine	TYR(B:135), GLY(B:144), TYR(B:138)	TYR(B:135), ASP(B:148
6WX4	Rutin	2GLU(D:252), TYR(D:252), SER(D:212),LEU(D:211)
	(-)-epicatechin 3,5-di-O-digallate (EC35G)	TYR(D:213), GLU(D:214), LYS(D:306)
	(-)-epigallocatechin gallate (EGCG)	164), TYR(D:273), 2GLY(D:163)	PRO(D:248)
	Apigenin glycoside	HIS(D:175), THR(D:74), TYR(D:154)	GLN(D:174)
	Flavonol 3-O-d-glucoside (FOG)	2SER(D:180), ASN(D:308), GLU(D:124)
	Myricetin 3-glucoside (M-G)	LEU(D:58), ASN(D:60), ASP(D:61)	GLN(D:30), PHE(D:31
	(-)-Epigallocatechin (EGC)	LYS(D:306), GLU(D:307), 2GLU(D:214), TYR(D:305)
	Kaempferol	ASP(D:164)
	(-)-epicatechin gallate (ECG)	2GLY(D:163), ASP(D:164), TYR(D:273), ARG(D:166)
	(+)-catechin	SER(D:212)
	(-)-epicatechin (EC)	LYS(D:306), 2GLU(D:307), TYR(D:305), TYR(D:213), GLU(D:214)
	Myricetin	GLY(D:266), THR(D:301), ASP(D:164)
	Kaempferol-3-O-glucoside	LYS(D:297), SER(D:212), THR(D:210)
	Quercetin	TYR(D:273)
	(-)-Epigallocatechin 3-(3-methyl-gallate) (3″Me-EGCG)	THR(D:301), ASP(D:164), TYR(D:273)
	Caffeoylquinic acid (CQA)	THR(D:257), TYR(D:213), TYR(D:251), GLU(D:214)
	Chlorogenic acid	2GLU(D:307), 2LYS(D:217), 2LYS(D:306), THR(D:257), TYR(D:251)
	Coumaric acid	GLU(D:252), LYS(D:217)	THR(D:257)
	Caffeic acid	LYS(D:217), SER(D:212)
	Gallic acid	GLU(D:214)
	Caffeine	ARG(D:116), THR(D:301)

Fig. 1

The 2D diagram showing the types of amino acid residues involved in the bond between the phytoconstituents in betel plant and the Mpro receptor of Sars-Cov-2. (A) PubChem ID 537,242, (B) PubChem ID 562,008, (C) PubChem ID 5,373,661, (D) PubChem ID 5,367,225, (E) PubChem ID 119,057,278, (F) PubChem ID 6,918,670, (G) PubChem ID 5,367,323, (H) PubChem ID 562,543, (I) PubChem ID 165,258, (J) PubChem ID 20,138,399.

Experimental Design, Materials, and Methods

Receptors and ligands selection

The selection of receptors is based on the information contained in the literature. Five essentials enzyme and proteins of SARS-CoV-2 selected as receptors in this study were spike ectodomain structure (open state) (PDB code: 6VYB), receptor-binding domain (RDB) (PDB code: 6YLA), main protease (Mpro) (PDB code: 6LU7), RNA-dependent RNA polymerase (RdRp) (PDB code: 6M71), and papain-like protease (PLpro) (PDB code: 6WX4). The phytoconstituents of betel leaf which serve as ligands were based on GC–MS data [16]. The GC–MS procedure was carried out following the research conducted by Tumilaar et al. [17]. The phytoconstituents of matcha green tea were selected based on a literature survey as listed in Table 2.

Receptors and ligands preparation

The structures of the receptor (Mpro) were retrieved from Protein Data Bank (http://www.rcsb.org) and opened in BIOVIA Discovery Studio Visualizer 2020 [18]. After removing the water molecules and native ligands, the receptor was saved in a .pdb format. All the structures of the ligands were retrieved from PubChem (http://pubchem.ncbi.nlm.nih.gov) in .sdf format. The files were converted into a .pdb format using Open Babel [19]. After adjusting the torque, the files were saved in .pdbqt format.

The docking process and visualization

Autudock Vina [20] was used in the docking analysis. The .pdbqt formats of ligands and receptors were copied into the Vina folder. Vina configuration was typed in notepad and saved as conf.txt. Vina program was performed in a command prompt mode. The most negative Gibbs’ free energy of binding indicated the best pose. The visualization of the interacting amino acids of the receptors with the ligands was performed in Biovia Discovery Studio 2020 [18].

Ethics Statement

The work did not involve the use of endangered species of wild flora.

Supplementary Data

Supplementary data to this article can be found at http://dx.doi.org/10.17632/w8h74c6hsy.1 and https://doi.org/10.17632/4dn4svm3jb.1.

CRediT Author Statement

Fatimawali: Conceptualization, Methodology, Data curtion, Writing - original draft, Writing – review & editing; Rizky Ramadhan Maulana: Software, Validation; Axl Laurens Lukas Windah: Software, Validation; Irma Febrianti Wahongan: Visualization, Investigation; Sefren Geiner Tumilaar: Visualization, Investigation; Ahmad Akroman Adam: Data curtion, Writing – review & editing; Billy Johnson Kepel: Data curtion, Writing – review & editing; Widdhi Bodhi: Visualization, Investigation; Trina Ekawati Tallei: Conceptualization, Methodology, Data curtion, Writing – review & editing, Supervision, Writing – review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article.

Subject	Biological sciences
Specific subject area	Bioinformatics, in silico analysis, molecular docking
Type of data	Tables and Figures
How data were acquired	AutoDock Vina and Biovia Discovery Studio Visualizer 2020
Data format	Raw and analyzedDirect URL to the data for betel plant: http://dx.doi.org/10.17632/s72rcpk82b.1Direct URL to the data for matcha green tea: http://dx.doi.org/10.17632/4dn4svm3jb.1
Parameters for data collection	In the drug discovery setting, Lipinski's rule of 5 predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight is greater than 500, and the calculated Log P (CLog P) is greater than 5.The docking score was obtained based on the most negative Gibbs’ free energy of binding generated using autodock Vina.The interactions between receptors’ amino acid residues and the ligands were visualized using Biovia Discovery Studio 2020.
Description of data collection	Betel plant phytoconstituents were obtained from GC–MS analysis; Phytoconstituents of matcha were collected from published articles listed in the references.
Data source location	The receptors’ structures were retrieved from https://www.rcsb.org/The ligands’ structures were retrieved from https://pubchem.ncbi.nlm.nih.gov/
Data accessibility	Repository name: Mendeley DataData identification number for betel plant: http://dx.doi.org/10.17632/s72rcpk82b.1Data identification number for matcha green tea: http://dx.doi.org/10.17632/4dn4svm3jb.1Direct URL to the data for betel plant: https://data.mendeley.com/datasets/s72rcpk82b/1Direct URL to the data for matcha green tea: https://data.mendeley.com/datasets/4dn4svm3jb/1
Related research article	T.E. Tallei, S.G. Tumilaar, A.A. Adam, Fatimawali, Evaluasi potensi polifenol Matcha sebagai agen anti-SARS-CoV-2 menggunakan pendekatan penambatan molekul, in: K. Wikantika, F.M. Dwivany, M.F. Ghazali, L.F. Yayusman, C. Novianti (Eds.), ForMIND Bunga Rampai 2020, ITB Press, Bandung, 2020, pp. 147–155.