TY - JOUR
T1 - Elucidation of the inhibitory activity of plant-derived SARS-CoV inhibitors and their potential as SARS-CoV-2 inhibitors
AU - Bello, Martiniano
AU - Hasan, Md Kamrul
N1 - Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - Several drugs are now being tested as possible therapies due to the necessity of treating SARS-CoV-2 infection. Although approved vaccines bring much hope, a vaccination program covering the entire global population will take a very long time, making the development of effective antiviral drugs an effective solution for the immediate treatment of this dangerous infection. Previous studies found that three natural compounds, namely, tannic acid, 3-isotheaflavin-3-gallate and theaflavin-3,3-digallate, are effective proteinase (3CLpro) inhibitors of SARS-CoV (IC50 <10 µM). Based on this information and due to the high sequence identity between SARS-CoV and SARS-CoV-2 3CLpro, these three compounds could be candidate inhibitors of SARS-CoV-2 3CLpro. This paper explores the structural and energetic features that guided the molecular recognition of these three compounds for dimeric SARS-CoV-2 and SARS-CoV 3CLpro, the functional state of this enzyme, using docking and MD simulations with the molecular mechanics-generalized-born surface area (MMGBSA) approach. Energetic analysis demonstrated that the three compounds reached good affinities in both systems in the following order: tannic acid > 3-isotheaflavin-3-gallate > theaflavin-3,3-digallate. This tendency is in line with that experimentally reported between these ligands and SARS-CoV 3CLpro. Therefore, tannic acid may have clinical usefulness against COVID-19 by acting as a potent inhibitor of SARS-CoV-2 3CLpro. Communicated by Ramaswamy H. Sarma.
AB - Several drugs are now being tested as possible therapies due to the necessity of treating SARS-CoV-2 infection. Although approved vaccines bring much hope, a vaccination program covering the entire global population will take a very long time, making the development of effective antiviral drugs an effective solution for the immediate treatment of this dangerous infection. Previous studies found that three natural compounds, namely, tannic acid, 3-isotheaflavin-3-gallate and theaflavin-3,3-digallate, are effective proteinase (3CLpro) inhibitors of SARS-CoV (IC50 <10 µM). Based on this information and due to the high sequence identity between SARS-CoV and SARS-CoV-2 3CLpro, these three compounds could be candidate inhibitors of SARS-CoV-2 3CLpro. This paper explores the structural and energetic features that guided the molecular recognition of these three compounds for dimeric SARS-CoV-2 and SARS-CoV 3CLpro, the functional state of this enzyme, using docking and MD simulations with the molecular mechanics-generalized-born surface area (MMGBSA) approach. Energetic analysis demonstrated that the three compounds reached good affinities in both systems in the following order: tannic acid > 3-isotheaflavin-3-gallate > theaflavin-3,3-digallate. This tendency is in line with that experimentally reported between these ligands and SARS-CoV 3CLpro. Therefore, tannic acid may have clinical usefulness against COVID-19 by acting as a potent inhibitor of SARS-CoV-2 3CLpro. Communicated by Ramaswamy H. Sarma.
KW - COVID-19
KW - SARS-CoV-2 3CLpro
KW - binding free energy
KW - molecular docking
KW - molecular dynamics simulation
UR - http://www.scopus.com/inward/record.url?scp=85107717845&partnerID=8YFLogxK
U2 - 10.1080/07391102.2021.1938234
DO - 10.1080/07391102.2021.1938234
M3 - Artículo
C2 - 34121618
AN - SCOPUS:85107717845
SN - 0739-1102
VL - 40
SP - 9992
EP - 10004
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 20
ER -