TABLE 5.

Interaction between bromelain and RBDs of the last frame MD simulation on amino acids that are important in the interaction between RBD and hACE2 (marked with italics font). The bold font indicates mutated amino acids.

RBD variants	RBD	Bromelain	Distance (Å)
	Residues	Residues	H-bonds	Salt-bridge	Nonbonded contacts
WT	Tyr449	Phe116	—	—	3.75
		Ser115	—	—	3.62
	Glu484	Asp132	2.73	—	3.88; 2.73; 3.61; 3.26
		Tyr133	—	—	3.76
		Gly134	—	—	3.58; 3.33; 3.89
		Lys162	2.90	2.90	3.51; 2.90; 3.72
	Gln493	Ile163	—	—	3.42; 3.81; 3.74; 3.88
		Val164	—	—	3.86
		Gly166	—	—	3.69
	Gly496	Ser339	—	—	3.88; 3.09; 3.76; 3.70; 3.84
	Gln498	Tyr228	2.79	—	3.74; 3.66; 3.85; 2.79
		Gln338	2.82	—	3.63; 3.21; 3.39; 2.82
		Ser339	—	—	3.65; 3.77
		Leu337	—	—	3.82
United Kingdom	Tyr449	Thr336	—	—	3.81; 3.60
		Tyr334	—	—	3.88; 3.89; 3.28
		Phe116	—	—	3.57; 3.65
	Gly446	Gln338	—	—	3.45; 3.61
	Glu484	Asp132	2.92	—	2.92; 3.64; 3.01
		Lys162	2.89	2.89	3.69; 3.36; 3.63; 2.89; 2.99; 3.09
		Tyr133	—	—	3.69; 3.84
		Gly134	—	—	3.81; 3.71
	Gln493	Ile163	—	—	3.23; 3.55; 3.67
		Val164	—	—	3.84; 3.25; 3.70; 3.09; 3.37; 3.74; 3.52
		Thr165	—	—	3.68; 3.74; 3.33; 3.67
		Gly166	—	—	3.58
	Gly496	Ser339	3.02	—	3.03
		Gln338	—	—	3.69; 3.88
	Gln498	Gln338	—	—	2.55; 3.77; 3.72; 3.80
	Tyr501	Ser339	—	—	3.78; 3.29; 3.54; 3.52; 3.11; 3.17; 2.95; 3.31
		Gln338	—	—	3.46; 3.83; 3.85
BR	Tyr449	Asp117	3.12	—
		Asn120	2.73	—	3.70; 3.61; 3.77; 2.73
		Ser115	—	—	3.86
		Asp117	—	—	3.12; 3.76; 3.24; 3.23; 3.80; 3.38
	Lys484	Asp132	2.75	—	3.77; 2.75; 3.73; 379
		Tyr133	—	—	3.65; 3.65; 3.68; 3.18
	Gln498	Gln338	3.13	—	3.70; 3.61; 3.83; 3.46; 3.75; 3.13
		Thr336	—	—	3.36
	Thr500	Gln338	—	—	3.88
	Tyr501	Ser339	3.14	—	3.70; 3.57; 3.14; 3.20
			—	—
SA	Tyr449	Ser115	2.85; 3.05	—	—
		Phe116	—	—	3.90
		Val114	—	—	3.72; 3.75; 3.84; 3.61; 3.69
		Ser115	—	—	3.39; 3.49; 3.56; 2.85; 3.68; 3.75; 3.05; 3.66
	Gly446	Gln338	2.69	—	3.48; 3.47; 3.51; 2.69
		Thr336	—	—	3.53; 3.69
	Lys484	Tyr133	—	—	3.58; 3.40; 3.86
	Gly496	Gln338	—	—	3.43; 3.39
	Gln498	Gln338	—	—	3.75; 3.68; 3.52; 3.59
		Thr230	—	—	3.68
	Tyr501	Ser339	2.75	—	3.04; 3.29; 3.39; 3.86; 3.68; 2.75; 3.18
		Gln338	—	—	3.56
United States	Tyr449	Thr336	—	—	3.60; 3.84
		Gln338	—	—	3.86; 3.12; 3.13; 3.07
	Gly446	Thr230	—	—	3.66; 3.40; 3.83; 3.75; 3.10; 2.68
		Gln338	—	—	3.85; 3.53
	Glu484	Asp132	2.69	—	3.89; 2.69; 3.71
		Tyr133	—	—	3.67; 3.29; 3.65; 3.45
		Lys162	3.01	2.90	3.44; 3.84; 3.01; 3.49; 3.36; 2.90
	Arg452	Asn249	—	—	3.84; 3.72; 2.84; 3.83; 3.81
		Gln250	—	—	3.89; 2.85
	Gln493	Val164	2.76	—	3.52; 3.54; 3.88; 3.42; 3.61; 3.50; 3.34; 3.80; 2.76
	Gly496	Ser339	—	—	3.66; 3.79; 3.21; 3.72; 3.72; 3.64
		Gln338	—	—	3.86
	Gln498	Gln338	3.01	—	3.01
		Thr230	—	—	3.84