Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;39(7):2659-2672.
doi: 10.1080/07391102.2020.1752310. Epub 2020 May 4.

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

Durgesh Kumar  1   2 , Kamlesh Kumari  3 , Abhilash Jayaraj  4 , Vinod Kumar  5 , Ramappa Venkatesh Kumar  6 , Sujata K Dass  7 , Ramesh Chandra  2 , Prashant Singh  1
Affiliations

Understanding the binding affinity of noscapines with protease of SARS-CoV-2 for COVID-19 using MD simulations at different temperatures

Durgesh Kumar et al. J Biomol Struct Dyn. 2021 Apr.

Abstract

The current outbreak of a novel coronavirus, named as SARS-CoV-2 causing COVID-19 occurred in 2019, is in dire need of finding potential therapeutic agents. Recently, ongoing viral epidemic due to coronavirus (SARS-CoV-2) primarily affected mainland China that now threatened to spread to populations in most countries of the world. In spite of this, there is currently no antiviral drug/ vaccine available against coronavirus infection, COVID-19. In the present study, computer-aided drug design-based screening to find out promising inhibitors against the coronavirus (SARS-CoV-2) leads to infection, COVID-19. The lead therapeutic molecule was investigated through docking and molecular dynamics simulations. In this, binding affinity of noscapines(23B)-protease of SARS-CoV-2 complex was evaluated through MD simulations at different temperatures. Our research group has established that noscapine is a chemotherapeutic agent for the treatment of drug resistant cancers; however, noscapine was also being used as anti-malarial, anti-stroke and cough-suppressant. This study suggests for the first time that noscapine exerts its antiviral effects by inhibiting viral protein synthesis.

Keywords: COVID-19; MD simulations; Protease of SARS-CoV-2; molecular docking; noscapine; screening.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Interaction of the residues of protease of coronavirus for COVID-19 with CMPD23B.
Figure 2.
Figure 2.
The 3D representations of top hit noscapines (CMPD23B).
Figure 3.
Figure 3.
Physiochemical space for oral bioavailability score enables a first glance at the drug-likeness of a molecule.
Figure 4.
Figure 4.
(a) & (c) shows the interaction of top hit molecule (23B) and N3 with protease of coronavirus for COVID-19 and (b) & (d) are Docked pose of hit molecule (23B) and N3 into the defined cavity.
Figure 5.
Figure 5.
Various molecular interactions between CMPD23B and protease of SARS-CoV-2 are observed in different favorable regions (a) Electrostatic favorable; (b) Steric favorable; (c) Hydrogen accepter favorable; and (d) Hydrogen donor favorable.
Figure 6.
Figure 6.
RMSD plot of protease of coronavirus for COVID-19 with and without CMPD23B as a function of time.
Figure 7.
Figure 7.
RMSF plot of protease of coronavirus for COVID-19 with and without CMPD23B at 100 ns time scale.
Figure 8.
Figure 8.
Number of hydrogen bonds of the complex of protease of coronavirus for COVID-19 with 23B as a function of time are retained or broken during simulation time scale 100 ns.
Figure 9.
Figure 9.
Enthalpy of the complex of protease of coronavirus for COVID-19 with 23B for MD simulation of 100 ns.
Figure 10.
Figure 10.
Non-isothermally RMSD plot for complex of protease of coronavirus for COVID-19 with 23B for MD simulations at 10 ns.
Figure 11.
Figure 11.
Non-isothermally RMSF plot for complex of protease of coronavirus for COVID-19 with 23B for MD simulations at 10 ns.
Figure 12.
Figure 12.
Number of HBs at 325 K for complex of protease of coronavirus for COVID-19 with 23B for MD simulations at 10 ns.
Figure 13.
Figure 13.
Number of HBs at 350 K for complex of protease of coronavirus for COVID-19 with 23B for MD simulations at 10 ns.
Figure 14.
Figure 14.
Number of HBs at 375 K for complex of protease of coronavirus for COVID-19 with 23B for MD simulations at 10 ns.
Figure 15.
Figure 15.
Enthalpy of the complex of protease of coronavirus of COVID-19 and 23B at different temperature for MD simulation of 10 ns.
See this image and copyright information in PMC

References

    1. Aaboud M., & ATLAS Collaboration. (2017). Determination of the strong coupling constant alpha s from transverse energy-energy correlations in multijet events at s = 8 TeV using the ATLAS detector. The European Physical Journal C, 77(12), 872, 1-34. doi. 10.1140/epjc/s10052-017-5442-0. - DOI - PMC - PubMed
    1. Aaboud M., ATLAS Collaboration, Aad G., Abbott B., Abdinov O., Abeloos B., Abhayasinghe D. K., Abidi S. H., AbouZeid O. S., Abraham N. L., Abramowicz H., Abreu H., Abulaiti Y., Acharya B. S., Adachi S., Adamczyk L., Adelman J., Adersberger M., Adiguzel A., … Zwalinski L. (2018). Probing the quantum interference between Singly and Doubly resonant top-quark production in pp collisions at sqrt[s] = 13 TeV with the ATLAS Detector. Physical Review Letters, 121(15), 152002. - PubMed
    1. Abbad A., Perera R. A., Anga L., Faouzi A., Minh N. N. T., Malik S. M. M. R., Iounes N., Maaroufi A., Van Kerkhove M. D., Peiris M., & Nourlil J. (2019). Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018. Eurosurveillance, 24(48), 1900244 10.2807/1560-7917.ES.2019.24.48.1900244 - DOI - PMC - PubMed
    1. Adasme-Carreno F., Munoz-Gutierrez C., Caballero J., & Alzate-Morales J. H. (2014). Performance of the MM/GBSA scoring using a binding site hydrogen bond network-based frame selection: The protein kinase case. Physical Chemistry Chemical Physics, 16(27), 14047–14055. 10.1039/C4CP01378F - DOI - PubMed
    1. Agarwal A., Nagi N., Chatterjee P., Sarkar S., Mourya D., Sahay R. R., & Bhatia R. (2020). Guidance for building a dedicated health facility to contain the spread of the 2019 novel coronavirus outbreak. Indian Journal of Medical Research. 10.4103/ijmr.IJMR_518_20 - DOI - PMC - PubMed