2 research outputs found
Structure-Based Discovery of the SARS-CoV‑2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine
Traditional
Chinese medicine (TCM) has been extensively
employed
for the treatment of coronavirus disease 2019 (COVID-19) caused by
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However,
there is demand for discovering more SARS-CoV-2 Mpro inhibitors with
diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this
study, comprehensive in silico and in vitro assays were utilized to
determine the potential inhibitors from TCM compounds against SARS-CoV-2
Mpro, which is an important therapeutic target for SARS-CoV-2. The
ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2
Mpro conformations identified 19 TCM compounds as promising candidates.
Further in vitro testing validated three compounds as inhibitors of
SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11,
7.56 ± 0.78, and 11.16 ± 0.26 μM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ±
1.25 μM, respectively. Molecular dynamics (MD) simulations indicated
that the three complexes remained stable over the last 100 ns of production
run. An analysis of the binding mode revealed that the active compounds
occupy different subsites (S1, S2, S3, and S4) of the active site
of SARS-CoV-2 Mpro via specific poses through noncovalent interactions
with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU
166, or GLN 189). Overall, this study provides evidence indicating
that the three natural products obtained from TCM could be further
used for anti-COVID-19 research, justifying the investigation of Chinese
herbal medicinal ingredients as bioactive constituents for therapeutic
targets
Structure-Based Discovery of the SARS-CoV‑2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine
Traditional
Chinese medicine (TCM) has been extensively
employed
for the treatment of coronavirus disease 2019 (COVID-19) caused by
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However,
there is demand for discovering more SARS-CoV-2 Mpro inhibitors with
diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this
study, comprehensive in silico and in vitro assays were utilized to
determine the potential inhibitors from TCM compounds against SARS-CoV-2
Mpro, which is an important therapeutic target for SARS-CoV-2. The
ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2
Mpro conformations identified 19 TCM compounds as promising candidates.
Further in vitro testing validated three compounds as inhibitors of
SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11,
7.56 ± 0.78, and 11.16 ± 0.26 μM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ±
1.25 μM, respectively. Molecular dynamics (MD) simulations indicated
that the three complexes remained stable over the last 100 ns of production
run. An analysis of the binding mode revealed that the active compounds
occupy different subsites (S1, S2, S3, and S4) of the active site
of SARS-CoV-2 Mpro via specific poses through noncovalent interactions
with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU
166, or GLN 189). Overall, this study provides evidence indicating
that the three natural products obtained from TCM could be further
used for anti-COVID-19 research, justifying the investigation of Chinese
herbal medicinal ingredients as bioactive constituents for therapeutic
targets