Table 2 Dynamics and energetics of the RdRp complexes with potential hits compared with investigational drugs and two reference compounds RTP and 2′-FdC.

From: In silico structural elucidation of RNA-dependent RNA polymerase towards the identification of potential Crimean-Congo Hemorrhagic Fever Virus inhibitors

Virtual hits AD Vina binding affinity (kcal/mol) RMSD ligand (Å) Time frame (ns) MM-GBSA H-Bond Interaction
ΔEvdw ΔEele ΔEMM ΔGp ΔGnp ΔGsol ΔGtol Atom pair a dinit (Å) b dMD (Å)
cmd1 −8.7 1.472 Initial (1 ns) −32.62 −24.97 −57.59 45.17 −4.38 40.79 −16.8 LIG:O3-Ser536:N 1.96 nd
Final (10 ns) −36.94 −27.59 −64.53 36.67 −5.63 31.04 −33.49 LIG:N3-Glu533:OE1 2.18 nd
Arg238:NH1-LIG:N1 nd 2.01
Arg238:NH1-LIG:O1 3.21 nd
LIG:N2-Phe534:O nd 2.89
LIG:N2-Leu234:O 2.18 nd
cmd2 −8.3 1.719 Initial (1 ns) −33.41 −19.56 −52.97 39.45 −4.51 34.94 −18.03 LIG:O2-Ser474O 2.86 nd
Final (10 ns) −40.72 −31.13 −71.85 46.01 −6.36 39.65 −32.2 LIG:O3-Ser474:OG nd 2.09
LIG:O3-Ser474:O nd 2.06
LIG:O3-Asp475:OD2 nd 2.75
Leu234:N-LIG:N4 nd 2.16
Ser536:N-LIG:O2 nd 1.71
cmd3 −9.8 1.822 Initial (1 ns) −34.84 −25.03 −59.87 42.12 −4.33 37.79 −22.08 Ser536:N-LIG:O3 nd 2.53
Final (10 ns) −38.91 −37.4 −76.31 45.32 −5.91 39.41 −36.9 Arg238:NH1-LIG:O1 3.25 2.1
LIG:N1-Asp316:OD1 3.33 nd
Ribavirin −6.4 1.32 Initial (1 ns) −17.99 −56.17 −74.16 66.23 −3.43 62.8 −11.36 Asn317:ND2-LIG:O3 nd 2.31
Final (10 ns) −17.72 −49.8 −67.52 58.04 −3.66 54.38 −13.14 Ser536:N-LIG:O4 3.1 nd
 – Ser536:N-LIG:O2 nd 2.74
 – LIG:O5-Asp316:OD2 2.77 nd
LIG:O3-Asp316:OD2 2.99 nd
LIG:O3-Ser474:OG 1.73 nd
LIG:O3-Asp475:OD2 1.55 nd
Favipiravir (T-705) −6.4 0.841 Initial (1 ns) −20.4 −17.53 −37.93 31.92 −2.77 29.15 −8.78 LIG:O2-Ser474:OG nd 2.81
Final (10 ns) −17.47 −22.01 −39.48 29.81 −2.71 27.1 −12.38 LIG:O2-Ser474:O nd 2.92
LIG:O2-Asp475:OD2 nd 2.83
Ser536:N-LIG:N1 3.11 2.13
Ser536:N-LIG:O2 2.84 nd
LIG:O2-Phe534:O 2.71 nd
LIG:O2-Glu533:OE1 2.96 nd
LIG:N3-Glu533:O nd 2.17
LIG:F-Gly432:N 3.03 nd
LIG:N3-Gly315:O 3.14 nd
LIG:N3-Asp316:OD2 3.16 nd
Arbidol −7 1.385 Initial (1 ns) −35.56 −8.35 −43.91 31.19 −4.28 26.91 −17 Ser536:N-LIG:O2 nd 2.83
Final (10 ns) −42.64 −11.64 −54.28 36.36 −5.38 30.98 −23.3 Asn317:ND2-LIG:O3 nd 2.81
Arg238:NH1-LIG:O1 3.26 nd
Ribavirin triphosphate (RTP) −6.2 1.435 Initial (1 ns) −10.9 −25.67 −36.57 31.16 −1.74 29.42 −7.15 LIG:O2-Ser474:OG nd 2.81
Final (10 ns) –20.16 −28.41 −48.58 34.72 −3.17 31.55 −17.02 LIG:O10-Asp475:OD2 3.11 2.20
LIG:O6-Asp475:OD2 2.98 2.77
LIG:O6-Asp476:OD1 3.11 2.19
Ser536:OG-LIG:O3 2.84 2.53
LIG:O13-Tyr535:N nd 2.41
LIG:N4-Glu533:O 2.96 2.11
LIG:N4-Gly315:O nd 2.89
LIG:N4-Tyr477:O 3.01 3.03
2′FdC −7.1 1.289 Initial (1 ns) −17.29 −40.10 −57.39 38.54 −2.91 35.63 −21.76 LIG:OG-Ser474:O3 2.14 2.03
Final (10 ns) −19.70 −42.10 −61.8 39.48 −2.35 37.13 −24.67 LIG:OG-Ser474:O4 nd 2.31
LIG:N-Ser475:O3 2.27 1.84
–  LIG:O3-Ser476:N 2.70 2.37
Ser536:N-LIG:O4 2.01 2.45
  1. initInitial distance of H-bond in Angstrom (Å) between atom pair.
  2. bDistance calculated after MD simulations for the H-bond between the same atom pair.