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Innovative Medicines & Omics Promising molecule against SARS-CoV-2 nucleocapsid

A

B

Figure 1. Results from molecular docking on the C-terminal Domain (N-CTD) of the nucleocapsid protein (N protein) of the SARS-CoV-2 virus.
(A) Comparison of the binding modes of compound BDBM6732 and its analog BDBM6732-bio2. The compound BDBM6732 is represented in blue, while
BDBM6732-bio2 is represented in pink. (B) Interaction diagrams illustrating the binding modes and interactions between the 6WZQ - BDBM6732 and
6WZQ - BDBM6732-bio2 complexes.

Table 2. In silico ADME ‑ Tox evaluation of the top five candidate compounds from high‑throughput virtual screening

BindingDB identifier HIA (%) VDSS (log) TR (ml/min/Kg) AMES MTD (mg/kg/dia) Hepatotoxicity
BDBM6732 99.53 −0.672 0. 565 Yes 0.463 Yes
BDBM9614 55.42 −0.603 0.391 No −0.234 Yes
BDBM15149 92.06 −0.099 0.416 Yes 0.391 Yes
BDBM15179 88.35 −0.199 0.110 No 0.431 No
BDBM7088 73.48 −0.015 0.280 No 0.438 No
Abbreviations: AMES: AMES toxicity test (mutagenesis); HIA: Human intestinal absorption; MTD: Maximum tolerated dose; TR: Total release;
VDSS: Volume of distribution at steady state.

[D], Glu280 [D], Thr282 [D], Gln281 [D], and Gln283 3.4. In silico ADME-Tox evaluation of analogs
[D]) (Table 3). It was noted that four out of the five proposed by bioisosterism
analogs formed a hydrogen bond with the amino acid The ADME-Tox properties for five analogs are as follows:
threonine, suggesting a potentially crucial role in the compound BDBM6732-bio1 has a high HIA of 98.74% and
enzyme’s catalytic activity. a moderate VDSS of −1.363, with a favorable TR of 0.452

Volume 1 Issue 1 (2024) 119 doi: 10.36922/imo.3731