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Innovative Medicines & Omics SARS-CoV-2 inhibition by quinolines

A B

C D

Figure 6. Anti-SARS-CoV-2 activity of 4-aminoquinoline derivatives in Calu-3 cells infected with Omicron variant. Percentage of viral replication
inhibition at 24 h (A and B) or 48 h (C and D) after treatment with compounds Q1a – Q4a (A and C) and Q1b – Q4b and Q1bS (B and D). Analysis was
conducted in comparison with the infected group. The variation presented by R ranged from 0.5 to 0.9 (n = 4).
2
Table 7. Best docking results obtained by a consensus from the DockThor and AutoDock Vina programs
Molecule Protein_Chain Interactions Score (kcal/mol) cKi (μM) a Minimum interaction
(program/pose) distance to C145:SG‑ (Å)
Q3a 6209_A (dockthor/1) HL: A191, F140, M165 −7.4877 3.7556 2.6214
PB: H41, H172
HB: F140, E166
SB: E166
Q1b 6209_A (dockthor/1) HL: C44, C145 −7.9683 1.6927 2.5647
PB: H41, H163, Q189, D187, Q166
Q2b 6209_A (dockthor/1) HL: C44, C145 −8.1297 1.6020 2.5537
PB: H41, G166
Q3b 6209_A (dockthor/3) PB: H41, H163, T45, R188 −8.1892 1.6918 2.5742
HL: C44, C145
Q4b 6209_A (dockthor/2) PB: H41, H164, S46, R188 −8.2128 1.1617 2,4405
HL: C44, C145, Y54
mefloquine 17362_A (Vina/2) HB: H41 −7.0983 21,1691 2.4246
molnupiravir 25647_A (Vina/7) HB: H41, N142, G143, S144, C145, D187 −6,6876 52,3210 2.3767
lopinavir 6209_A (Vina/3) HB: H41, H163 e C145 −8,5603 47,9367 2,3123
Note: cKi (µM): Theoretical concentration required to produce half of the maximum inhibition of the enzyme. 78
a
Abbreviations: HB: Hydrogen bond; HL: Hydrophobic bond; PB: Polar bond; SB: Salt bridge.
been reported, particularly in response to public health The inhibitory action of hydroxychloroquine on
emergencies such as COVID-19. 46-48 Regarding their SARS-CoV-2 has been extensively documented in the
specific antiviral activity, studies in the literature have literature. 49-51 Nonetheless, its mode of action, which
shown that chemical analogs of compounds belonging to involves disrupting endosomal acidification essential for
the 4-aminoquinoline family, such as quinine, chloroquine, cathepsin proteolytic processes, only effectively prevents
and hydroxychloroquine, have been tested for their viral entry into cells lacking the TMPRSS2 receptor. This
antiviral effects against various viral diseases. 20 specific interaction accounts for the drug’s lack of efficacy

Volume 1 Issue 1 (2024) 96 doi: 10.36922/imo.3442