Fig 1.
(A) The structures of the S protein trimer (electrostatic potential surface area (PDB ID: 6vxx)),S1(A), S2(A), S1(B), S2(B), S1(C) and S2(C) are shown in cyan, gray, blue, orange, magenta, and yellow-green, respectively. (B) Schematic of the SARS-CoV-2 S protein primary structure, colored by domain.
Table 1.
The highest binding energy of drug molecules with the S protein in molecular docking simulations.
Fig 2.
(A) Binding mode of the interaction of tizoxanide with the S protein. The S protein trimer is shown as a transparent red surface, S1(A), S1(B), and S2(C) are shown as cyan, blue, and yellow-green cartoons, respectively, and tizoxanide is shown as green spheres. (B) Binding mode of tizoxanide with the S protein. S1(A), S1(B), and S2(C) are shown as cyan, blue, and yellow-green surfaces, respectively, and tizoxanide is shown as green sticks. (C) The key residues that may form potential interactions with tizoxanide (green sticks) and polar interactions are indicated by blue dotted lines.
Fig 3.
(A) Binding mode of the interactions of bictegravir and dolutegravir with the S protein. The S protein trimer is shown as a transparent red surface, S1(A), S1(B), and S2(B) are shown as cyan, blue, and orange cartoons, respectively, and bictegravir and dolutegravir are shown as green spheres. (B) and (D) Binding mode of bictegravir and dolutegravir (green) with the S protein. S1(A) and S1(B) are shown as cyan and blue surfaces, and bictegravir and dolutegravir are shown as green sticks. (C) and (E) The key residues that may form potential interactions with bictegravir and dolutegravir (green sticks) and polar interactions are indicated by blue dotted lines.
Fig 4.
(A) Binding mode of the interaction of arbidol with the S protein. The S protein trimer is shown as a transparent red surface; S1(A), S2(A), and S2(B) are shown as cyan cartoons; and arbidol is shown as a green sphere. (B) Binding mode of arbidol (green) with the S protein. S1(A), S2(A), and S2(B) are shown as cyan surfaces, and arbidol is shown as a green stick. (C) The key residues that may form potential interactions with arbidol (green stick) and polar interactions are indicated by blue dotted lines.
Fig 5.
(A) and (C) The amino acid residues that surround the phenol group and nitro group of tizoxanide (green). (B) and (D) The amino acid residues surrounding the phenol and nitro groups are shown as green surfaces.
Fig 6.
Strategy for further structural optimization of tizoxanide.
Fig 7.
Molecular mode results for Ti-1(A), Ti-2(B), and Ti-3(C) with the S protein and the key residues that may form potential interactions with compounds Ti-1, Ti-2 and Ti-3.
Fig 8.
(A) The amino acid residues that surround the trifluorophenyl and difluorophenyl moieties of bictegravir (green) and dolutegravir (blue-green). (B) The amino acid residues surrounding the trifluorophenyl and difluorophenyl moieties are shown as green surfaces.
Fig 9.
Strategy for further structural optimization of bictegravir and dolutegravir.
Fig 10.
Molecular mode results for BD-1(A), BD-2(B), and BD-3(C) with the S protein and the key residues that may form potential interactions with compounds BD-1, BD-2, and BD-3.
Fig 11.
(A) The polar residues that surround the Br of arbidol (green). (B) The H-binding region consists of polar residues, which are shown as a transparent surface. (C) The hydrophobic residues that surround the N-methyl group. (D) The arbidol–hydrophobic residue complex; the hydrophobic residues are shown as a transparent surface.
Fig 12.
Strategy for further structural optimization of arbidol.
Fig 13.
Molecular mode results for Ar-1 (A), Ar-2 (B), and Ar-3 (C) with the S protein and the key residues that may form potential interactions with compounds Ar-1, Ar-2, and Ar-3.