In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment

Table 1 Energy of affinity of ligand/receptor complexes obtained in molecular docking and characteristics of interactions between Remdesivir and angiotensin-converting enzyme 2

Receptor/ligand complex	Energy of affinity (kcal/moL)
ACE2/Remdesivir	-8.8
ACE2/Osetalmivir	-5.7
ACE2/Atazanavir	-3.9
Fibrinogen/Remdesivir	-8.5
Fibrinogen/Osetalmivir	-6.3
Fibrinogen/Atazanavir	-4
Prothrombin/Remdesivir	-8.4
Prothrombin/Osetalmivir	-6
Prothrombin/Atazanavir	-4.1

ACE2: Angiotensin-converting enzyme 2.

Table 2 Characteristics of interactions between Remdesivir and angiotensin-converting enzyme 2

	Interaction1	Distance (Å)	Bond type
ACE2/Remdesivir	N-18:GLU-398	3.3	Hydrogen bond
	O-29:HIS-378	2.5	Hydrogen bond
	O-30:ALA-348	2.4	Hydrogen bond
	O-30:ALA-348	3.3	Hydrogen bond
	O-34:ALA-348	3.2	Hydrogen bond
	O-36:ASP-350	2.3	Hydrogen bond
	O-37:ASP-350	3.4	Hydrogen bond
	O-40:ARG-393	3.5	Hydrogen bond

¹Remdesivir: Residue. ACE2: Angiotensin-converting enzyme 2; O: Oxygen; N: Nitrogen; GLU: Glutamate; ALA: Alanine; ASP: Aspartate; ARG: Arginine.

Table 3 Energy of affinity of ligand/receptor complexes obtained in silico

Ligand/receptor complex	Energy of affinity (kcal/moL)
Remdesivir/tissue factor (thromboplastin)	-8.2
Remdesivir/Factor V (proacelerin)	-6.8
Remdesivir/Factor VII (proconvertin)	-7.0
Remdesivir/Factor IX (anti-hemophilic B)	-6.4
Remdesivir/Factor X	-9.6
Remdesivir/Factor XI	-8.3

Table 4 Binding characteristics of Remdesivir/Factor II and Remdesivir/Factor VII complexes

Complex	Interaction1	Distance (Å)	Bond type
Remdesivir/Factor II II (protrombin)	O-23: GLY-548	2	Hydrogen bond
	O-3: GLY-548	3.2	Hydrogen bond
	N-15: ASN-463	2.6	Hydrogen bond
	O-35: SER-525	2.4	Hydrogen bond
	O-35: HIS-363	2.6	Hydrogen bond
	O-3: GLY-550	2	Hydrogen bond
Remdesivir/Factor VII (Proconvertin)	O-3: ASP-60	3.5	Hydrogen bond
	O-3: THR-98	3.1	Hydrogen bond
	O-2: THR-98	3.6	Hydrogen bond
	O-2: GLY-97	3.2	Hydrogen bond
	N-17: GLY-216	3.1	Hydrogen bond

¹Remdesivir: Residue. O: Oxygen; N: Nitrogen; ASP: Aspartate; ASN: Asparagine; THR: Threonine; SER: Serine; HIS: Histidine; GLY: Glycine.

Table 5 Binding characteristics of Remdesivir/Factor X complex

Interaction1	Distance (Å)	Bond type
N-18: ALA-190	3.33	Hydrogen bond
N-18: GLY-219	3.44	Hydrogen bond
N-23: GLY-193	2.3	Hydrogen bond
N-23: GLN-192	3.35	Hydrogen bond
O-29: SER-195	2.92	Hydrogen bond
O-29: SER-195	2.29	Hydrogen bond
O-29: SER-214	2.78	Hydrogen bond
O-29: HIS-57	2.92	Hydrogen bond
O-29: HIS-57	2.53	Hydrogen bond
O-30: HIS-57	2.93	Hydrogen bond
Aromatic ring C-3: TRP-215	4.21	Pi-stacking
Aromatic ring C-3: TRP-215	4.03	Pi-stacking
Aromatic ring C-3: TYR-99	5.06	Pi-stacking
Aromatic ring C-3: PHE-174	5.13	Pi-stacking
Aromatic ring C-8: CYS-191 and GLN-192	4.57	Amide pi-stacking
Aromatic ring C-31: CYS-191 and GLN-192	4.31	Amide pi-stacking
Aromatic ring C-8: TRP-215 and GLY-216	4.53	Amide pi-stacking
Aromatic ring C-31: TRP-215 and GLY-216	4.89	Amide pi-stacking
C-2: LYS-96	3.96	Alkyl
C-2: TYR-60	5.05	Pi-alkyl
C-2: PHE-94	5.39	Pi-alkyl
C-2: PHE-94	4.87	Pi-alkyl
Aromatic ring C-8: CYS-220	5.47	Pi-alkyl
Aromatic ring C-31: ALA-190	5.29	Pi-alkyl

¹Remdesivir: Residue. O: Oxygen; N: Nitrogen; C: Carbon; ALA: Alanine; GLY: Glycine; SER: Serine; HIS: Histidine; TRP: Tryptophan; TYR: Tyrosine; PHE: Phenylalanine; CYS: Cysteine; LYS: Lysine.