Targeting omicron and other reported SARS-CoV-2 lineages by potent inhibitors of main protease 3CL Mpro: Molecular simulation analysis

Saeed, Aamir; Ahmad, Basharat; Majaz, Sidra; Nouroz, Faisal; Ahmad, Ashfaq; Xie, Yingqiu

doi:10.1016/j.jinf.2022.02.012

Cited by 3 publications

(2 citation statements)

References 10 publications

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“…These results are quite similar with the results produced in the present work for the first cluster of FA, as the binding energies do not differ significantly and there is one common residue involved in hydrogen bonding (Thr190). Another work reported a binding energy of −10.63 kcal/mol and hydrogen bonds with residues Leu141, Gly143, Ser144, Cys145, His163, and Glu166 [ 62 ] while the orientation of FA in the active is identical to the one observed in the second cluster for FA in this work. In accordance with the present results, a docking score of −6.0 kcal/mol was reported for FA when the Autodock Vina and PDB structure 6W63 were used [ 63 ].…”

Section: Resultssupporting

confidence: 63%

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

2022

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The main protease (Mpro) of SARS-CoV-2 is an appealing target for the development of antiviral compounds, due to its critical role in the viral life cycle and its high conservation among different coronaviruses and the continuously emerging mutants of SARS-CoV-2. Ferulic acid (FA) is a phytochemical with several health benefits that is abundant in plant biomass and has been used as a basis for the enzymatic or chemical synthesis of derivatives with improved properties, including antiviral activity against a range of viruses. This study tested 54 reported FA derivatives for their inhibitory potential against Mpro by in silico simulations. Molecular docking was performed using Autodock Vina, resulting in comparable or better binding affinities for 14 compounds compared to the known inhibitors N3 and GC376. ADMET analysis showed limited bioavailability but significantly improved the solubility for the enzymatically synthesized hits while better bioavailability and druglikeness properties but higher toxicity were observed for the chemically synthesized ones. MD simulations confirmed the stability of the complexes of the most promising compounds with Mpro, highlighting FA rutinoside and compound e27 as the best candidates from each derivative category.

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Section: Resultssupporting

confidence: 63%

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

2022

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“…This can be explained by the conserved bind pattern between P132H 3CLpro in complex with Nirmatrelvir under structural simulation. 258 , 272 , 298 , 299 GRL-0617 was reported to be a novel drug targeting the PLpro of SARS-CoV-2. Despite the status as a preclinical study, the relatively high efficacy against ancestral strain infection in vitro (EC 50 1.9–2.5 μM—WT) may suggest its bright future for further investigation.…”

Section: Molecular Characteristics Of Sequence and The Encoded Protei...mentioning

confidence: 99%

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Sun

Xie

et al. 2022

Sig Transduct Target Ther

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The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.

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Novel small-molecule inhibitors of SARS-CoV-2 main protease with nanomolar antiviral potency

Zhang,

Zhou,

Peng

et al. 2024

Journal of Infection

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Targeting omicron and other reported SARS-CoV-2 lineages by potent inhibitors of main protease 3CL Mpro: Molecular simulation analysis

Cited by 3 publications

References 10 publications

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

The Inhibitory Potential of Ferulic Acid Derivatives against the SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and ADMET Evaluation

Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants

Novel small-molecule inhibitors of SARS-CoV-2 main protease with nanomolar antiviral potency

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