Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the h ACE2 Receptor.
Ahmed A. Al-Karmalawy,Mohammed A. Dahab,Ahmed M. Metwaly,Sameh S. Elhady,Eslam B. Elkaeed,Ibrahim H. Eissa,Khaled M. Darwish +6 more
Reads0
Chats0
TLDR
In this paper, the authors considered drug repurposing as an attractive approach that can facilitate the drug discovery process by reusing existing pharmaceuticals to treat illnesses other than their primary indications.Abstract:
The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs). Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.read more
Citations
More filters
Journal ArticleDOI
Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights
Dalia Elebeedy,Walid F. Elkhatib,Ahmed Kandeil,Aml Ghanem,Omnia Kutkat,Radwan Alnajjar,Radwan Alnajjar,Marwa A. Saleh,Ahmed I. Abd El Maksoud,Ingy Badawy,Ahmed A. Al-Karmalawy +10 more
TL;DR: Six compounds were screened for their anti-SARS-CoV-2 activities against both the spike (S) and main protease (Mpro) receptors using molecular docking studies and showed very promising virucidal activity with a most prominent inhibitory effect on viral adsorption rather than its replication.
Journal ArticleDOI
Calendulaglycoside A Showing Potential Activity Against SARS-CoV-2 Main Protease: Molecular Docking, Molecular Dynamics, and SAR Studies.
Ahmed A. Zaki,Thomas Schleicher,Ahmed Ashour,Sameh S. Elhady,Khaled M. Darwish,Ahmed A. Al-Karmalawy +5 more
TL;DR: A promising SAR is clarified responsible for the antiviral activity against the SARS-CoV-2 Mpro and the design of new drug candidates targeting it as well is clarified and could be promising for fast examining the previously isolated triterpenes both pre-clinically and clinically for the treatment of COVID-19.
Journal ArticleDOI
Computational Insights on the Potential of Some NSAIDs for Treating COVID-19: Priority Set and Lead Optimization.
Ayman Abo Elmaaty,Mohammed I. A. Hamed,Muhammad I. Ismail,Eslam B. Elkaeed,Hamada S. Abulkhair,Muhammad Khattab,Ahmed A. Al-Karmalawy +6 more
TL;DR: In this article, 40 FDA-approved drugs were evaluated through molecular docking against the main protease of SARS-CoV-2, including sulfinpyrazone 2, indomethacin 3, and auranofin 4.
Journal ArticleDOI
Bioactive Polyphenolic Compounds Showing Strong Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus 2
Ahmed Kandeil,Ahmed Mostafa,Omnia Kutkat,Yassmin Moatasim,Ahmed A. Al-Karmalawy,Adel A. Rashad,Ahmed E. Kayed,Azza E Kayed,Rabeh El-Shesheny,Ghazi Kayali,Mohamed A. Ali +10 more
TL;DR: In this article, the in vitro antiviral activities of curcumin, hesperidin, and quercetin against SARS-CoV-2 compared to hydroxychloroquine and determine their mode of action.
Journal ArticleDOI
Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies.
Heba A. El Gizawy,Sylvia A. Boshra,Ahmed Mostafa,Sara H. Mahmoud,Muhammad I. Ismail,Aisha A. Alsfouk,Azza T. Taher,Ahmed A. Al-Karmalawy +7 more
TL;DR: In this article, four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence.
References
More filters
Journal ArticleDOI
VMD: Visual molecular dynamics
TL;DR: VMD is a molecular graphics program designed for the display and analysis of molecular assemblies, in particular biopolymers such as proteins and nucleic acids, which can simultaneously display any number of structures using a wide variety of rendering styles and coloring methods.
Journal ArticleDOI
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
TL;DR: An N⋅log(N) method for evaluating electrostatic energies and forces of large periodic systems is presented based on interpolation of the reciprocal space Ewald sums and evaluation of the resulting convolutions using fast Fourier transforms.
Journal ArticleDOI
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
Journal ArticleDOI
LINCS : A linear constraint solver for molecular simulations
TL;DR: Although the derivation of the algorithm is presented in terms of matrices, no matrix matrix multiplications are needed and only the nonzero matrix elements have to be stored, making the method useful for very large molecules.
Journal ArticleDOI
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2
Alexander E. Gorbalenya,Susan C. Baker,Ralph S. Baric,Raoul J. de Groot,Christian Drosten,Anastasia A. Gulyaeva,Bart L. Haagmans,Chris Lauber,Andrey M. Leontovich,Benjamin W. Neuman,Dmitry Penzar,Stanley Perlman,Leo L.M. Poon,Dmitry V. Samborskiy,Igor A. Sidorov,Isabel Sola,John Ziebuhr +16 more
TL;DR: The independent zoonotic transmission of SARS-CoV and SARS -CoV-2 highlights the need for studying viruses at the species level to complement research focused on individual pathogenic viruses of immediate significance.