In Silico Mutagenesis-Based Remodelling of SARS-CoV-1 Peptide (ATLQAIAS) to Inhibit SARS-CoV-2: Structural-Dynamics and Free Energy Calculations

Khan, Abbas; Umbreen, Shaheena; Hameed, Asma; Fatima, Rida; Zahoor, Ujala; Babar, Zainib; Waseem, Muhammad; Hussain, Zahid; Rizwan, Muhammad; Zaman, Nasib; Ali, Shahid; Suleman, Muhammad; Shah, Abdullah; Ali, Liaqat; Ali, Syed Shujait; Wei, Dong‐Qing

doi:10.1007/s12539-021-00447-2

Cited by 21 publications

(10 citation statements)

References 48 publications

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“… Baell and Holloway, 2010 , de Wit et al, 2016 , El-Missiry et al, 2021 , Houston and Walkinshaw, 2013 , Khan et al, 2021 , Khan et al, 2021 , Treutter, 2006 , Trott and Olson, 2010 , Yang et al, 2020 , Yang et al, 2020 .…”

Section: Uncited Referencesmentioning

confidence: 99%

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

et al. 2022

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Section: Uncited Referencesmentioning

confidence: 99%

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

et al. 2022

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“…Molecular dynamics (MD) simulation of the vaccine-TLR complex was performed to check the stability of the complex using AMBER20 simulation package for 20ns (48,49). The parameters were used as previously used by Abbas et al (50,51).…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Evaluation of the Whole Proteome of Achromobacter xylosoxidans to Identify Vaccine Targets for mRNA and Peptides-Based Vaccine Designing Against the Emerging Respiratory and Lung Cancer-Causing Bacteria

Khan

Abdullah

Toor³

et al. 2022

Front. Med.

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Achromobacter xylosoxidans is a rod-shaped Gram-negative bacterium linked with causing several infections which mostly includes hematological malignancies. It has been recently reported to be associated with the development and progression of lung cancer and is an emerging respiratory disease-causing bacterium. The treatment of individuals infected with A. xylosoxidans bacteremia is difficult due to the fact that this pathogen has both intrinsic and acquired resistance mechanisms, typically resulting in a phenotype of multidrug resistance (MDR). Efforts are needed to design effective therapeutic strategies to curtail the emergence of this bacterium. Computational vaccine designing has proven its effectiveness, specificity, safety, and stability compared to conventional approaches of vaccine development. Therefore, the whole proteome of A. xylosoxidans was screened for the characterization of potential vaccine targets through subtractive proteomics pipeline for therapeutics design. Annotation of the whole proteome confirmed the three immunogenic vaccine targets, such as (E3HHR6), (E3HH04), and (E3HWA2), which were used to map the putative immune epitopes. The shortlisted epitopes, specific against Cytotoxic T Lymphocytes, Helper T-cell Lymphocytes, and linear B-Cell, were used to design the mRNA and multi-epitopes vaccine (MEVC). Initial validations confirmed the antigenic and non-allergenic properties of these constructs, followed by docking with the immune receptor, TLR-5, which resulted in robust interactions. The interaction pattern that followed in the docking complex included formation of 5 hydrogen bonds, 2 salt bridges, and 165 non-bonded contacts. This stronger binding affinity was also assessed through using the mmGBSA approach, showing a total of free binding energy of −34.64 kcal/mol. Further validations based on in silico cloning revealed a CAI score of 0.98 and an optimal percentage of GC contents (54.4%) indicated a putatively higher expression of the vaccine construct in Escherichia coli. Moreover, immune simulation revealed strong antibodies production upon the injection of the designed MEVC that resulted in the highest peaks of IgM+ IgG production (>3,500) between 10 and 15 days. In conclusion the current study provide basis for vaccine designing against the emerging A. xylosoxidans, which demands further experimental studies for in vitro and in vivo validations.

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“…The MM-PBSA/GBSA is used for calculation of binding free energies. The MMPBSA/ GBSA approach is based on the combination of continuous solvent fashions and molecular mechanical energies [27]. For these calculations; MMPBSA.py a python script was used to calculate the free energy of reference compound and selected compounds.…”

Section: Binding Free Energy Calculationmentioning

confidence: 99%

Deciphering the impact of Mutations in the RBD of the Omicron Variant (BA.2) with Medicinal compound to disrupt the RBD-hACE2 complex using computational approaches

Akter

2022

Preprint

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Human health and the economy have been greatly affected by COVID-19 emergence, that originated from SARS-CoV-2. Just after the very first case of COVID-19 emerged, a number of variants have been reported with severe risk of reinfection and evading immunity. Overall, 30 mutations in the spike protein have been reported in SARS-CoV-2 (BA.2) variant in India and South Africa, while half among these 30 mutations are receptor-binding domain which have spread rapidly throughout the world. The modern world has been swaddled by this extremely contagious Omicron variant, while it is rapidly mutating that is alarming and need to be addressed. Due to antibodies-escaping activity, the micro molecule that can inhibit it, are required to be discovered. Therefore, we focused on the computational drug designing, including Pharmacophore based virtual Screening, MD simulation to identity the novel small molecular inhibitor that stop hACE2 to bind with Receptor Binding Domain (RBD). We screened three medicinal compound databases, North-East African, North African and East African We carried out a multi-step screening approach that identified three compounds, which are (10R)-3',4'-dihydro-1,4,8,3',8',9'-hexahydroxy-3,3-dimethyl-[10,7'-bianthracene]-9,1'(10H,2'H)-dione (C1), 6'-(4-hydroxy cinnamoyl) arbutin (C2), and Acacetin 7-glucoside (C3), that are effective for omicron RBD variant due its excellent antiviral capabilities. Then PAIN assay interference, computation bioactivity prediction, binding free energy and dissociation constant was used to validate the top hits, indicated the good anti-viral activity. To summarize, we aimed to identify and design novel medication therapies that could be utilized in combating with newly discovered omicron strain of SARS-CoV-2.

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In Silico Mutagenesis-Based Remodelling of SARS-CoV-1 Peptide (ATLQAIAS) to Inhibit SARS-CoV-2: Structural-Dynamics and Free Energy Calculations

Cited by 21 publications

References 48 publications

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols

Evaluation of the Whole Proteome of Achromobacter xylosoxidans to Identify Vaccine Targets for mRNA and Peptides-Based Vaccine Designing Against the Emerging Respiratory and Lung Cancer-Causing Bacteria

Deciphering the impact of Mutations in the RBD of the Omicron Variant (BA.2) with Medicinal compound to disrupt the RBD-hACE2 complex using computational approaches

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