Combined deep learning and molecular docking simulations approach identifies potentially effective FDA approved drugs for repurposing against SARS-CoV-2

Anwaar, Muhammad Umer; Adnan, Farjad; Abro, Asma; Khan, Rayyan Azam; Rehman, Asad Ur; Osama, Muhammad; Rainville, Christopher; Kumar, Suresh; Sterner, David E.; Javed, Saad; Jamal, Syed Babar; Baig, Ahmadullah; Shabbir, Muhammad Raffey; Ahsan, Waseh; Butt, Tauseef R.; Assir, Muhammad Zaman Khan

doi:10.1016/j.compbiomed.2021.105049

Cited by 24 publications

(10 citation statements)

References 56 publications

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“…In particular, docking analysis revealed that iturin and anidulafungin might target ACE2-spike protein interaction (Chowdhury et al, 2021; Ahamad et al, 2022 ). Moreover, based on the in silico results, anidulafungin is also believed to interact with a number of SARS-CoV-2 viral proteins ( Dey et al, 2021 ; Anwaar et al, 2022 ). A possible explanation of the absence of the antiviral action of caspofungin ( Table 2 ) despite its pronounced inhibitory effect on liposome fusion ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs

et al. 2023

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Section: Resultsmentioning

confidence: 99%

Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs

et al. 2023

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“…A previous study showed that FAD could enhance the antiviral activity of interferon-alpha-2a against the influenza virus type A and Herpes simplex virus 1 [ 26 ]. Other studies have also suggested FAD as an anti-SARS-CoV-2 agent by interacting with its spike proteins [ 27 ], 3-chymotrypsin-like protease [ 28 ], and papain-like protease (PLpro) [ 29 ]. Using both computational and experimental methods, FAD was proved to have inhibitory activity against the SARS-CoV-2 PLPro with the IC 50 of 12.39 μM [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies have also suggested FAD as an anti-SARS-CoV-2 agent by interacting with its spike proteins [ 27 ], 3-chymotrypsin-like protease [ 28 ], and papain-like protease (PLpro) [ 29 ]. Using both computational and experimental methods, FAD was proved to have inhibitory activity against the SARS-CoV-2 PLPro with the IC 50 of 12.39 μM [ 29 ]. Another study showed the lung protectability of FAD in H5N1 virus-induced lung injury [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study

Lam

Tran²,

Thanh

et al. 2022

IJMS

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The World Health Organization declared monkeypox a global public health emergency on 23 July 2022. This disease was caused by the monkeypox virus (MPXV), which was first identified in 1958 in Denmark. The MPXV is a member of the Poxviridae family, the Chordopoxvirinae subfamily, and the genus Orthopoxvirus, which share high similarities with the vaccinia virus (the virus used to produce the smallpox vaccine). For the initial stage of infection, the MPXV needs to attach to the human cell surface glycosaminoglycan (GAG) adhesion molecules using its E8 protein. However, up until now, neither a structure for the MPXV E8 protein nor a specific cure for the MPXV exists. This study aimed to search for small molecules that inhibit the MPXV E8 protein, using computational approaches. In this study, a high-quality three-dimensional structure of the MPXV E8 protein was retrieved by homology modeling using the AlphaFold deep learning server. Subsequent molecular docking and molecular dynamics simulations (MDs) for a cumulative duration of 2.1 microseconds revealed that ZINC003977803 (Diosmin) and ZINC008215434 (Flavin adenine dinucleotide-FAD) could be potential inhibitors against the E8 protein with the MM/GBSA binding free energies of −38.19 ± 9.69 and −35.59 ± 7.65 kcal·mol−1, respectively.

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“…Interestingly, most PPs investigated were previously studied against SARS-CoV-2. For example, flavin mononucleotide and flavin adenine dinucleotide have been suggested as good 3CL pro and RNA-dependent RNA polymerase inhibitors, respectively [22,44]. Riboflavin and sofosbuvir were shown to be suitable inhibitors of the spike protein S1 domain/ACE2 and RNA-dependent RNA polymerase [45][46][47].…”

Section: The Binding Free Energiesmentioning

confidence: 99%

Molecular Docking and Dynamics Investigations for Identifying Potential Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2: Repurposing of Approved Pyrimidonic Pharmaceuticals for COVID-19 Treatment

Elzupir

2021

Molecules

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This study demonstrates the inhibitory effect of 42 pyrimidonic pharmaceuticals (PPs) on the 3-chymotrypsin-like protease of SARS-CoV-2 (3CLpro) through molecular docking, molecular dynamics simulations, and free binding energies by means of molecular mechanics–Poisson Boltzmann surface area (MM-PBSA) and molecular mechanics–generalized Born surface area (MM-GBSA). Of these tested PPs, 11 drugs approved by the US Food and Drug Administration showed an excellent binding affinity to the catalytic residues of 3CLpro of His41 and Cys145: uracil mustard, cytarabine, floxuridine, trifluridine, stavudine, lamivudine, zalcitabine, telbivudine, tipiracil, citicoline, and uridine triacetate. Their percentage of residues involved in binding at the active sites ranged from 56 to 100, and their binding affinities were in the range from −4.6 ± 0.14 to −7.0 ± 0.19 kcal/mol. The molecular dynamics as determined by a 200 ns simulation run of solvated docked complexes confirmed the stability of PP conformations that bound to the catalytic dyad and the active sites of 3CLpro. The free energy of binding also demonstrates the stability of the PP–3CLpro complexes. Citicoline and uridine triacetate showed free binding energies of −25.53 and −7.07 kcal/mol, respectively. Therefore, I recommend that they be repurposed for the fight against COVID-19, following proper experimental and clinical validation.

show abstract

Combined deep learning and molecular docking simulations approach identifies potentially effective FDA approved drugs for repurposing against SARS-CoV-2

Cited by 24 publications

References 56 publications

Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs

Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs

Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study

Molecular Docking and Dynamics Investigations for Identifying Potential Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2: Repurposing of Approved Pyrimidonic Pharmaceuticals for COVID-19 Treatment

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