In Silico Designing of a Multitope Vaccine against Rhizopus microsporus with Potential Activity against Other Mucormycosis Causing Fungi

Soltan, Mohamed A.; Eldeen, Muhammad Alaa; Elbassiouny, Nada; Kamel, Hasnaa L.; Abdelraheem, Kareem M.; El-Gayyed, Hanaa Abd; Gouda, Ahmed M.; Sheha, Mohammed F.; Fayad, Eman; Ali, Ola A. Abu; Ghany, Khalid Abd El; El-damasy, Dalia A.; Darwish, Khaled M.; Elhady, Sameh S.; Sileem, Ashraf E.

doi:10.3390/cells10113014

Cited by 22 publications

(20 citation statements)

References 92 publications

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“…Molecular dynamics simulation was perused for evaluating the relative epitope-TLR motions, conformation-time evolution, and thermodynamic stability under near-physiological conditions (51). Using GROMACS-5.1.4 and CHARMM36m forcefield, the constructed models of the multiepitope vaccine in complex with either TLR-4 or TLR-8 were individually simulated through 100 nsall atom molecular dynamics as previously reported (24,52). Protein complexes were solvated within TIP3P water and under periodic boundary conditions keeping the protein complex at 10 Å marginal distances from the box margins.…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

“…More recently, a new field that studies the immunological data and the tools that were developed to handle these data has been named immunoinformatics (19). This novel approach was applied to develop a vaccine construct against many pathogens, starting from bacteria such as Moraxella catarrhalis (20) and Escherichia coli (21) to viruses such as Nipah virus (22) and fungi such as Candida auris (23) and Mucormycosis causing fungi (24).…”

Section: Introductionmentioning

confidence: 99%

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Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Soltan

Abdulsahib²,

Amer

et al. 2022

Front. Immunol.

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Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

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Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Soltan

Abdulsahib²,

Amer

et al. 2022

Front. Immunol.

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“…These convergence and stability findings were consistent with reported studies investigating small molecule’s affinity to the SARS-CoV-2 M pro target through molecular docking and dynamics simulations. The depicted PAD and X77-related RMSD tones were as steady as those for investigated top-active anti-M pro beta-blocker agents, angiotensin II receptor blockers, marine polyketides, scalarane sesterterpenes, and natural flavonoid aglycones [ 60 , 61 , 67 , 68 , 69 ]. The latter confirmed the thermodynamic stability of PAD at the M pro pocket.…”

Section: Resultsmentioning

confidence: 84%

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics

Abdallah

El-Halawany

Darwish

et al. 2022

Plants

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Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (MPRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand–target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 MPRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 MPRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 MPRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC50/IC50 = 1.33 and CC50/IC50 = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC50/IC50 = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC50/IC50 = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 MPRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19.

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“…They showed that, Dedicated Outdoor Air System model reduced the CO 2 emissions to 691 tons, with a potential of reducing heating, ventilation, and air conditioning and whole-building energy use by 37% and 16%, respectively in the hot arid climate, with a return on investment of about 6% [ 76 ]. Another recent study by Soltan et al, demonstrated the first ever developed multitope vaccine against Mucormycosis causing fungi based on the immunoinformatic approach [ 77 ]. Thus, proper precautions and care in patient health and maintenance of hygienic and controlled environment are necessary to manage Mucormycosis effectively.…”

Section: Precautions and Care To Manage Mucormycosismentioning

confidence: 99%

Risks of mucormycosis in the current Covid-19 pandemic: a clinical challenge in both immunocompromised and immunocompetent patients

Monika

Chandraprabha

2022

Mol Biol Rep

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Mucormycosis, also called “Black Fungus”, is a new cause for worry in the current Coronavirus disease 2019 (covid-19) pandemic. Mucormycosis is devasting due to its high rate of morbidity and mortality which is a great cause of concern. Mucormycosis, in general, affects immunocompromised patients including diabetic, people with malignancies, organ and stem cell transplants and people affected with pandemic diseases like covid-19. Diagnosis of Mucormycosis is often delayed either due to clinical complications or misdiagnosed as symptoms of other diseases, especially covid-19. This could delay the treatment protocol which results in the failure of treatment. Mortality rate due to secondary infections in covid-19 patients with uncontrolled diabetics and who are on steroid therapy can soon reach 100% if diagnosis and treatment doesn’t happen on timely basis. Risk of Mucormycosis is not just in immunosuppressed patients, but immunocompetent people with late diagnosis are also prone to infection. In view of this, we present a comprehensive review on risks of Mucormycosis in immunocompromised and immunocompetent patients highlighting the epidemiology, forms of Mucormycosis, immune response against Mucorales, difficulties in diagnosis and challenges in treatment of Mucormycosis, with emphasis on covid-19 associated Mucormycosis. Importantly, we have discussed the precautions and care to effectively manage Mucormycosis in immunocompromised and immunocompetent patients. Thus, current review helps clinicians in understanding various risk factors in both immunocompromised (especially covid-19 patients) and immunocompetent patients which is critical in managing Mucormycosis in current covid-19 pandemic.

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In Silico Designing of a Multitope Vaccine against Rhizopus microsporus with Potential Activity against Other Mucormycosis Causing Fungi

Cited by 22 publications

References 92 publications

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine

Bio-Guided Isolation of SARS-CoV-2 Main Protease Inhibitors from Medicinal Plants: In Vitro Assay and Molecular Dynamics

Risks of mucormycosis in the current Covid-19 pandemic: a clinical challenge in both immunocompromised and immunocompetent patients

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