The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies

Aminah, Nanik Siti; Abdjan, Muhammad İkhlas; Wardana, Andika Pramudya; Kristanti, Alfinda Novi; Siswanto, Imam; Rakhman, Khusna Arif; Takaya, Yoshiaki

doi:10.1039/d1ra07584e

Cited by 4 publications

(2 citation statements)

References 64 publications

(57 reference statements)

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“…While the reason for the inhibitory effect of the tested compounds towards 3CL pro is not clearly understood, the strength of hydrogen bonding interactions between ligands and 3CL pro or forming the salt bridge with His163 along hydrogen bonds may explain differential inhibitory effects 47 , 48 . We have performed the MD simulation, post-analysis process, and enzymatic assay to understand the chemical mechanism.…”

Section: Discussionmentioning

confidence: 99%

Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CLPro) activity in silico and in vitro

Dakpa,

Kumar,

Nelen

et al. 2023

Sci Rep

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Despite the remarkable development of highly effective vaccines, including mRNA-based vaccines, within a limited timeframe, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not been entirely eradicated. Thus, it is crucial to identify new effective anti-3CLPro compounds, pivotal for the replication of SARS-CoV-2. Here, we identified an antcin-B phytosterol-like compound from Taiwanofungus camphoratus that targets 3CLPro activity. MTT assay and ADMET prediction are employed for assessing potential cytotoxicity. Computational molecular modeling was used to screen various antcins and non-antcins for binding affinity and interaction type with 3CLPro. Further, these compounds were subjected to study their inhibitory effects on 3CLPro activity in vitro. Our results indicate that antcin-B has the best binding affinity by contacting residues like Leu141, Asn142, Glu166, and His163 via hydrogen bond and salt bridge and significantly inhibits 3CLPro activity, surpassing the positive control compound (GC376). The 100 ns molecular dynamics simulation studies showed that antcin-B formed consistent, long-lasting water bridges with Glu166 for their inhibitory activity. In summary, antcin-B could be useful to develop therapeutically viable drugs to inhibit SARS-CoV-2 replication alone or in combination with medications specific to other SARS-CoV-2 viral targets.

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Section: Discussionmentioning

confidence: 99%

Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CLPro) activity in silico and in vitro

Dakpa,

Kumar,

Nelen

et al. 2023

Sci Rep

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show abstract

“…Other natural product sources screened by docking and MM/PB(GB)SA against Mpro were flavonoid-based phytochemical constituents of calendula officinalis, phytochemicals in Indian ginseng, food compounds, marine natural polyketides, malaria-box compounds, cressa cretica compounds, strychnos nux-vomica products, ayurvedic compounds, moringa oleifera compounds, withania sp. products, stilbenolignans from plants, acridinedione analogs, alkaloids from justicia adhatoda , tea plant products, neem compounds, turmeric compounds, echinacea angustifolia products, Withania somnifera (ashwagandha) products, cyperus rotundus Linn products, salvia plebeia products, lichen compounds, curcuma longa products, and polyphenols from broussonetia papyrifera . − …”

Section: Methods and Approachesmentioning

confidence: 99%

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Gao¹,

Wang²,

Chen³

et al. 2022

Chem. Rev.

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Despite tremendous efforts in the past two years, our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), virus–host interactions, immune response, virulence, transmission, and evolution is still very limited. This limitation calls for further in-depth investigation. Computational studies have become an indispensable component in combating coronavirus disease 2019 (COVID-19) due to their low cost, their efficiency, and the fact that they are free from safety and ethical constraints. Additionally, the mechanism that governs the global evolution and transmission of SARS-CoV-2 cannot be revealed from individual experiments and was discovered by integrating genotyping of massive viral sequences, biophysical modeling of protein–protein interactions, deep mutational data, deep learning, and advanced mathematics. There exists a tsunami of literature on the molecular modeling, simulations, and predictions of SARS-CoV-2 and related developments of drugs, vaccines, antibodies, and diagnostics. To provide readers with a quick update about this literature, we present a comprehensive and systematic methodology-centered review. Aspects such as molecular biophysics, bioinformatics, cheminformatics, machine learning, and mathematics are discussed. This review will be beneficial to researchers who are looking for ways to contribute to SARS-CoV-2 studies and those who are interested in the status of the field.

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Developing semisynthesis methods for neglected tropical diseases

Majhi,

Manickam

2024

Semisynthesis of Bioactive Compounds and Their Biological Activities

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The dolabellane diterpenes as potential inhibitors of the SARS-CoV-2 main protease: molecular insight of the inhibitory mechanism through computational studies

Abstract: An investigation on dolabellane derivatives to understand their potential in inhibiting the SARS-CoV-2 main protease (3CLpro) using an in silico approach.

Cited by 4 publications

References 64 publications

Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CLPro) activity in silico and in vitro

Antcin-B, a phytosterol-like compound from Taiwanofungus camphoratus inhibits SARS-CoV-2 3-chymotrypsin-like protease (3CLPro) activity in silico and in vitro

Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2

Developing semisynthesis methods for neglected tropical diseases

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