A dynamic simulation study of FDA drug from zinc database against COVID-19 main protease receptor

Mathpal, Shalini; Joshi, Tushar; Sharma, Priyanka; Joshi, Tanuja; Pundir, Hemlata; Pande, Veena; Chandra, Subhash

doi:10.1080/07391102.2020.1821785

Cited by 23 publications

(14 citation statements)

References 38 publications

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“…It is a standard measure of the deviation of the atoms from its original position. Furthermore, it can be used to assess the flexibility of the backbone atoms of the protein structure as well as the ligand [ 66 ]. A thorough study of the RMSF curves of the free proteins (Mpro, PLPro, Spike) and their complexes showed RMSF fluctuations of all amino acids located in the active site of the proteins.…”

Section: Resultsmentioning

confidence: 99%

Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study

Reza¹,

Tk²,

Baildya³

et al. 2022

Microbial Pathogenesis

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Section: Resultsmentioning

confidence: 99%

Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study

Reza¹,

Tk²,

Baildya³

et al. 2022

Microbial Pathogenesis

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“…The docking results confirm the identification of five, four, and five compounds binding to 3CL pro , PL pro , and RdRp, respectively, on the basis of a cluster analysis, higher docking scores than the reference compounds (Supplementary Table 1), and key residue interactions. Since molecular docking does not involve physiological conditions and real-time behavior of the proteinligand interactions, selected compounds were subjected to MD simulations to check their stability and binding affinity towards respective target proteins (Blunt et al, 2016;Mathpal et al, 2020). The structural analysis of the SARS-CoV-2 3CL pro crystal structure bound with α-ketoamide revealed the inhibitor targets of His41, Phe140, Gly143, Cys145, His164, and Glu166 through hydrogen bonds.…”

Section: Discussionmentioning

confidence: 99%

“…The betacoronavirus class includes SARS coronavirus (SARS-CoV), Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV), and the COVID-19 causative agent SARS-CoV-2 (Pal et al, 2020). In the past, before the discovery of SARS-CoV-2, six types of coronaviruses were known to cause diseases in humans, including SARS-CoV and MERS-CoV (Mathpal et al, 2020;Zhu et al, 2020). The genome analysis of SARS-CoV-2 sequences revealed that it shares a 79% sequence identity with SARS-CoV and 89% with bat SARS-CoV (Lu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Computational Simulations Identified Marine-Derived Natural Bioactive Compounds as Replication Inhibitors of SARS-CoV-2

et al. 2021

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The rapid spread of COVID-19, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide health emergency. Unfortunately, to date, a very small number of remedies have been to be found effective against SARS-CoV-2 infection. Therefore, further research is required to achieve a lasting solution against this deadly disease. Repurposing available drugs and evaluating natural product inhibitors against target proteins of SARS-CoV-2 could be an effective approach to accelerate drug discovery and development. With this strategy in mind, we derived Marine Natural Products (MNP)-based drug-like small molecules and evaluated them against three major target proteins of the SARS-CoV-2 virus replication cycle. A drug-like database from MNP library was generated using Lipinski’s rule of five and ADMET descriptors. A total of 2,033 compounds were obtained and were subsequently subjected to molecular docking with 3CLpro, PLpro, and RdRp. The docking analyses revealed that a total of 14 compounds displayed better docking scores than the reference compounds and have significant molecular interactions with the active site residues of SARS-CoV-2 virus targeted proteins. Furthermore, the stability of docking-derived complexes was analyzed using molecular dynamics simulations and binding free energy calculations. The analyses revealed two hit compounds against each targeted protein displaying stable behavior, binding affinity, and molecular interactions. Our investigation identified two hit compounds against each targeted proteins displaying stable behavior, higher binding affinity and key residual molecular interactions, with good in silico pharmacokinetic properties, therefore can be considered for further in vitro studies.

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“…Therefore, M pro plays crucial roles in both viral propagation viral genome replication. The development of an M pro inhibitor could obstruct viral amplification ( Mathpal et al, 2020 ; Tripathi et al, 2020 ; Mahmud et al, 2021d ). The cysteine protease-based M pro contains a catalytic dyad in the active center.…”

Section: Discussionmentioning

confidence: 99%

Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach

et al. 2021

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Coronavirus disease 2019 (COVID-19) is a potentially lethal and devastating disease that has quickly become a public health threat worldwide. Due to its high transmission rate, many countries were forced to implement lockdown protocols, wreaking havoc on the global economy and the medical crisis. The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus for COVID-19, represent an effective target for the development of a new drug/vaccine because it is well-conserved and plays a vital role in viral replication. Mpro inhibition can stop the replication, transcription as well as recombination of SARS-CoV-2 after the infection and thus can halt the formation of virus particles, making Mpro a viable therapeutic target. Here, we constructed a phytochemical dataset based on a rigorous literature review and explored the probability that various phytochemicals will bind with the main protease using a molecular docking approach. The top three hit compounds, medicagol, faradiol, and flavanthrin, had binding scores of −8.3, −8.6, and −8.8 kcal/mol, respectively, in the docking analysis. These three compounds bind to the active groove, consisting of His41, Cys45, Met165, Met49, Gln189, Thr24, and Thr190, resulting in main protease inhibition. Moreover, the multiple descriptors from the molecular dynamics simulation, including the root-mean-square deviation, root-mean-square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond analysis, confirmed the stable nature of the docked complexes. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed a lack of toxicity or carcinogenicity for the screened compounds. Our computational analysis may contribute toward the design of an effective drug against the main protease of SARS-CoV-2.

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A dynamic simulation study of FDA drug from zinc database against COVID-19 main protease receptor

Cited by 23 publications

References 38 publications

Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study

Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study

Computational Simulations Identified Marine-Derived Natural Bioactive Compounds as Replication Inhibitors of SARS-CoV-2

Screening of Potent Phytochemical Inhibitors Against SARS-CoV-2 Main Protease: An Integrative Computational Approach

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