Inhibitors of SARS-3CL<sup>pro</sup>: Virtual Screening, Biological Evaluation, and Molecular Dynamics Simulation Studies

Mukherjee, Prasenjit; Shah, Falgun; Desai, Prashant; Avery, Mitchell A.

doi:10.1021/ci1004916

Cited by 47 publications

(36 citation statements)

References 109 publications

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“…For example, SARS PLpro cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUbLys48 products [13,14]. SARS-3CLpro is a cysteine protease indispensable to the viral life cycle [15]. Coronavirus spike protein uses angiotensinconverting enzyme 2 as a receptor to help the virus enter cells [16].…”

Section: Introductionmentioning

confidence: 99%

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Zhang¹,

Zhang³

et al. 2020

Journal of Integrative Medicine

409

395

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a b s t r a c tObjective: In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods: There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results: Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion: Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.

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Section: Introductionmentioning

confidence: 99%

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Zhang¹,

Zhang³

et al. 2020

Journal of Integrative Medicine

409

395

View full text Add to dashboard Cite

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“…Total energy of hydrogen atoms, ions, and water molecules were minimized in 1500 steps using the steepest descent method to under 300 kJ/mol. The other MD setting was as reported before at a neutral pH (29,30).…”

Section: Molecular Dynamic Simulation Settingmentioning

confidence: 99%

Lopinavir; A Potent Drug against Coronavirus Infection: Insight from Molecular Docking Study

Dayer

Taleb-Gassabi

Dayer

2017

Arch Clin Infect Dis

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Background: The severe acute respiratory syndrome (SARS) is a life threatening viral infection caused by a positive, single stranded RNA virus from the enveloped coronaviruse family. Associated with fever, cough, and respiratory complications, the illness causes more than 15% mortality worldwide. So far, there is no remedy for the illness except supportive treatments. However, the main viral proteinase has recently been regarded as a suitable target for drug design against SARS infection due to its vital role in polyproteins processing necessary for coronavirus reproduction. Objectives: The present in silico study was designed to evaluate the effects of anti HIV-1 proteases inhibitors, approved for clinical applications by US FDA, on SARS proteinase inhibition. Methods: In the present study, docking and molecular dynamic experiments were applied to examine the effect of inhibitors on coronavirus proteinase under physiological conditions of similar pH, temperature, and pressure in aqueous solution. Hex software version 5.1 and GROMACS 4.5.5 were used for docking analysis throughout this work. Results:The calculated parameters such as RMSD, RMSF, MSD, dipole moment, diffusion coefficient, binding energy, and binding site similarity indicated effective binding of inhibitors to SARS proteinase resulting in their structural changes, which coincide with proteinase inhibition. Conclusions:The inhibitory potency of HIV 1 protease inhibitors to cronovirus proteinase was as follows: LPV > RTV > APV > TPV > SQV. Lopinavir and Saquinavir were the most and the least powerful inhibitors of cronovirus proteinase, respectively.

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“…Many of the inhibitors identified to date, such as peptidomimetic (Ghosh et al, 2007), TG-0205221 (Yang et al, 2006), ketones (Shao et al, 2008), and pyrimidines (Ramajayam et al, 2010), have previously been reviewed in detail (Mukherjee et al, 2011;Zhao et al, 2013a;Zhao et al, 2013b;Adedeji and Sarafianos, 2014). Therefore, we here focus only on the most recent Kim et al, 2015 progress in inhibitor and drug discovery.…”

Section: Main Proteasementioning

confidence: 99%

Recent progress in the discovery of inhibitors targeting coronavirus proteases

et al. 2016

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Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. The fatal outbreak of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) highlights the threat posed by this unique virus subfamily. However, no specific drugs have been approved to treat CoV-associated diseases to date. The CoV proteases, which play pivotal roles in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, are attractive targets for drug design. This review summarizes the recent advances in biological and structural studies, together with the development of inhibitors targeting CoV proteases, particularly main proteases (M(pro)s), which could help develop effective treatments to prevent CoV infection.

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Inhibitors of SARS-3CL^pro: Virtual Screening, Biological Evaluation, and Molecular Dynamics Simulation Studies

Cited by 47 publications

References 109 publications

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Lopinavir; A Potent Drug against Coronavirus Infection: Insight from Molecular Docking Study

Recent progress in the discovery of inhibitors targeting coronavirus proteases

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Inhibitors of SARS-3CLpro: Virtual Screening, Biological Evaluation, and Molecular Dynamics Simulation Studies

Cited by 47 publications

References 109 publications

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

Lopinavir; A Potent Drug against Coronavirus Infection: Insight from Molecular Docking Study

Recent progress in the discovery of inhibitors targeting coronavirus proteases

Contact Info

Product

Resources

About

Inhibitors of SARS-3CL^pro: Virtual Screening, Biological Evaluation, and Molecular Dynamics Simulation Studies