Drug discovery and development targeting the life cycle of SARS-CoV-2

Xu, Yechun; Jiang, Hualiang

doi:10.1016/j.fmre.2021.01.013

Cited by 16 publications

(7 citation statements)

References 105 publications

(103 reference statements)

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“…Several strategies have been used to develop antiviral drugs for SARS-CoV-2; to date, some drugs are effective against this virus, but only some neutralizing antibodies and remdesivir have been approved by the US FDA [ 9 ]. The drug development against SARS-CoV-2 is mainly focused on interrupting the virus's life cycle by blocking its interaction with the host [ 10 , 11 ]. An increasing number of recent studies have used computational methods for identifying new drug targets or drug repurposing candidates.…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein

Shrestha

Marahatha

Basnet

et al. 2022

Advances in Pharmacological and Pharmaceutical Sciences

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The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral entry into the host cells, hence inhibiting the virus from fusing and infecting the host. This study determined the binding interactions of 36 flavonoids along with two FDA-approved drugs against the spike protein receptor-binding domain of SARS-CoV-2 through molecular docking and molecular dynamics (MD) simulations. In addition, the molecular mechanics generalized Born surface area (MM/GBSA) approach was used to calculate the binding-free energy (BFE). Flavonoids were selected based on their in vitro assays on SARS-CoV and SARS-CoV-2. Our pharmacokinetics study revealed that cyanidin showed good drug-likeness, fulfilled Lipinski’s rule of five, and conferred favorable toxicity parameters. Furthermore, MD simulations showed that cyanidin interacts with spike protein and alters the conformation and binding-free energy suited. Finally, an in vitro assay indicated that about 50% reduction in the binding of hACE2 with S1-RBD in the presence of cyanidin-containing red grapes crude extract was achieved at approximately 1.25 mg/mL. Hence, cyanidin may be a promising adjuvant medication for the SARS-CoV-2 spike protein based on in silico and in vitro research.

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Section: Introductionmentioning

confidence: 99%

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein

Shrestha

Marahatha

Basnet

et al. 2022

Advances in Pharmacological and Pharmaceutical Sciences

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“…Based on viral studies conducted in clinical trials by the U.S. Food and Drug Administration, 2020, the use of combination therapy has been highly recommended such as lopinavir, ritonavir in combination with chloroquine, hydroxychloroquine, and interferon-alpha since they have exhibited potential in the treatment of SARS-CoV-2 infection [ 55 , 56 ]. Similarly, the combination therapy with natural products has delivered promising results while targeting the specific stages of viral life cycle critical for its survival [ 57 , 58 ]. It is therefore indispensable to expand the treatment options and include medicinal plants in our research.…”

Section: Discussionmentioning

confidence: 99%

Senna makki and other active phytochemicals: Myths and realities behind covid19 therapeutic interventions

Zaman

Parvaiz²,

Farid³

et al. 2022

PLoS ONE

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This study aims to investigate the binding potential of chemical compounds of Senna in comparison with the experimentally tested active phytochemicals against SARS-CoV-2 protein targets to assist in prevention of infection by exploring multiple treatment options. The entire set of phytochemicals from both the groups were subjected to advanced computational analysis that explored functional molecular descriptors from a set of known medicinal-based active therapeutics followed by MD simulations on multiple SARS-CoV-2 target proteins. Our findings manifest the importance of hydrophobic substituents in chemical structures of potential inhibitors through cross-validation with the FDA-approved anti-3CLpro drugs. Noteworthy improvement in end-point binding free energies and pharmacokinetic profiles of the proposed compounds was perceived in comparison to the control drug, vizimpro. Moreover, the identification of common drug targets namely; AKT1, PTGS1, TNF, and DPP4 between proposed active phytochemicals and Covid19 using network pharmacological analysis further substantiate the importance of medicinal scaffolds. The structural dynamics and binding affinities of phytochemical compounds xanthoangelol_E, hesperetin, and beta-sitosterol reported as highly potential against 3CLpro in cell-based and cell-free assays are consistent with the computational analysis. Whereas, the secondary metabolites such as sennosides A, B, C, D present in higher amount in Senna exhibited weak binding affinity and instability against the spike protein, helicase nsp13, RdRp nsp12, and 3CLpro. In conclusion, the results contravene fallacious efficacy claims of Senna tea interventions circulating on electronic/social media as Covid19 cure; thus emphasizing the importance of well-examined standardized data of the natural products in hand; thereby preventing unnecessary deaths under pandemic hit situations worldwide.

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“…Convalescent plasma, monoclonal antibodies spike binding peptide, and small molecules blocked viral entry. Chlorpomazine and chloroquine inhibited endocytosis, niclosamide and chloroquine increased pH of viral endosome, and arbidol inhibited relasing viral genome (Muhammed, 2020;Su et al, 2021;Riva et al, 2020;Mei and Tan, 2021). Viral replication inhibitors involved lopinavir, remdesivir, favipiravir, and emetine inhibited catalization process of viral protease, such as Plpro, 3CLPro, and RdRp (Shyr et al, 2020;Cui et al, 2020;Su et al, 2021;Riva et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Chlorpomazine and chloroquine inhibited endocytosis, niclosamide and chloroquine increased pH of viral endosome, and arbidol inhibited relasing viral genome (Muhammed, 2020;Su et al, 2021;Riva et al, 2020;Mei and Tan, 2021). Viral replication inhibitors involved lopinavir, remdesivir, favipiravir, and emetine inhibited catalization process of viral protease, such as Plpro, 3CLPro, and RdRp (Shyr et al, 2020;Cui et al, 2020;Su et al, 2021;Riva et al, 2020). Viral entry targeted proteins, viral genome replications protein, and protease were an effective therapy and management for COVID-19 (Shyr et al, 2020;Song et al, 2021;Muhammed, 2020;Mei and Tan, 2021;Fig et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A New Complex Design of Fe (II) Isoleucine Dithiocarbamate as a Novel Anticancer and Antivirus against SARSCOV-2 (COVID-19)

Irfandi

Riswandi

Raya

et al. 2022

Asian Pac J Cancer Prev

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Background: This study was carried out to synthesize a new complex of Fe(II) with isoleucine dithiocarbamate ligand and to determine its potential as an anticancer and antiviral agent for SARSCOV-2. Methods: The synthesized complexes were then characterized by UV-vis and FT-IR spectroscopy and their melting points. The value of the conductivity of the complex compound is also determined. Anti-cancer activity was tested in vitro and molecular docking. Its potential as an antiviral against SARSCOV-2 was also carried out by molecular docking. Pharmacokinetics/ ADMET properties were also carried out on the complex. Result: Spectral results showed the successful synthesis of Fe(II) isoleucine dithiocarbamate complex. The complex produced UV-vis spectra at 268 and 575 nm, and the IR data at 399-599 cm-1 showed the coordination between the Fe(II) atoms with sulphur, nitrogen and oxygen of the isoleucine dithiocarbamate ligand. Fe(II) isoleucine dithiocarbamate had a cytotoxicity effect on the MCF-7 cell line (IC 50 =613 µg/mL). The complex significantly caused morphological changes in the breast cancer cell line, finally leading to cell apoptosis. Conclusion: Cytotoxic test of Fe(II) isoleucine dithiocarbamate showed moderate anticancer activity on MCF-7 cancer cells and showed antiviral activity against SARSCOV-2 by interfering with spike glycoprotein -ACE2 receptors, and inhibiting major proteases and 3Clpro.

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Drug discovery and development targeting the life cycle of SARS-CoV-2

Cited by 16 publications

References 105 publications

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein

Senna makki and other active phytochemicals: Myths and realities behind covid19 therapeutic interventions

A New Complex Design of Fe (II) Isoleucine Dithiocarbamate as a Novel Anticancer and Antivirus against SARSCOV-2 (COVID-19)

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