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. 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.

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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.
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