- I'm working in the Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt as a Lecturer then Assoc... moreI'm working in the Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt as a Lecturer then Associate Professor starting from the year 2013. My interest in Molecular Biophysics pushes me to work in Structural Bioinformatics and Drug Design to find potent inhibitors against viral and pathogenic fungal proteins utilizing in silico techniques. During the past 6 years, I focused my research on polymerase protein due to its vital role in the life cycle of the pathogenic organisms. I studied also other proteins like protease, estrogen receptors and kinases. Currently, I'm working on fungal CotH kinase family proteins crucial for Mucormycosis virulence and the unfolded protein response master chaperone protein, GRP78.edit
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A novel series of bis-[1,3,4]thiadiazolimines, and bis-thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1′-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α-haloketones,... more
A novel series of bis-[1,3,4]thiadiazolimines, and bis-thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1′-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α-haloketones, respectively. Docking studies were applied to test the binding affinity of the synthesized products against the Mpro of SARS-CoV-2. The best compound, 5h, has average binding energy (−7.50 ± 0.58 kcal/mol) better than that of the positive controls O6K and N3 (−7.36 ± 0.34 and −6.36 ± 0.31 kcal/mol). Additionally, the docking poses (H-bonds and hydrophobic contacts) of the tested compounds against the Mpro using the PLIP web server were analyzed.
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During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved... more
During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before. Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp. The present in silico study suggests the dual inhibition potential of the recommended drugs and compounds against SARS-CoV-2 and R. oryzae RdRps.
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Different SARS-CoV-2 new variants emerged and spread during the past few months, sparking infections and death counts. The new variant B.1.617 (delta variant) sparked in India in the past few months, causing the highest records. The... more
Different SARS-CoV-2 new variants emerged and spread during the past few months, sparking infections and death counts. The new variant B.1.617 (delta variant) sparked in India in the past few months, causing the highest records. The B.1.617 variant of SARS-CoV-2 has the double mutations E484Q and L452R on its spike Receptor Binding Domain (RBD). The first mutation is like the reported South African and the Brazilian variants (501.V2 and B.1.1.248). This mutation lies in the region C480-C488, which we predicted before to be recognized by the host-cell receptor; Glucose Regulated Protein 78 (GRP78). In the current study, we test the binding affinity of the host-cell receptor GRP78 to the delta variant spike RBD using molecular docking and molecular dynamics simulations of up to 100 ns. Additionally, the ACE2-RBD is tested by protein–protein docking. The results reveal equal average binding affinities of the GRP78 against wildtype and delta variant spikes. This supports our previous pr...
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Since the first appearance of the coronavirus disease-2019 (COVID-19) in Wuhan, China, in December 2019, it has been spreading globally with devastating ramifications. The lack of anti-COVID-19 treatment to date warrants urgent research... more
Since the first appearance of the coronavirus disease-2019 (COVID-19) in Wuhan, China, in December 2019, it has been spreading globally with devastating ramifications. The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that are capable of targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). The latter plays a fundamental role in mediating viral replication and transcription, rendering it an attractive drug target. In this study, twenty six novel halogenated, heterocyclic compounds, which can inhibit Mpro, were tested by molecular docking combined with molecular dynamics simulation. Three compounds showed the highest binding affinity to the protein active site and their binding modes coincide with that of Nelfinavir. The binding of the halogenated compounds to Mpro may inhibit the replication and transcription...
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<b>Supplementary Table 1</b><br><br>Binding affinity of the drug molecules against SARS-CoV-2 Nsp15. <b>Supplementary Figure 1</b>. The redocking of the citrate into Nsp15 (PDB ID: 6W01 chain A). the... more
<b>Supplementary Table 1</b><br><br>Binding affinity of the drug molecules against SARS-CoV-2 Nsp15. <b>Supplementary Figure 1</b>. The redocking of the citrate into Nsp15 (PDB ID: 6W01 chain A). the citrate moieties are colored according to the color code at the bottom of the figure.
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The Coronavirus Diseases 2019 (COVID-19) seriously affecting human health all over the world. More than 107 M people are reported positive for SARS-CoV-2, the virus causing COVID-19 pneumonia, from which +2.3 M died. Nucleotide Inhibitors... more
The Coronavirus Diseases 2019 (COVID-19) seriously affecting human health all over the world. More than 107 M people are reported positive for SARS-CoV-2, the virus causing COVID-19 pneumonia, from which +2.3 M died. Nucleotide Inhibitors (NI) have promising results in terms of its efficacy against different viral polymerases, including the Hepatitis C Virus (HCV) Non-Structural Protein 5 B (NS5B) RNA dependent RNA polymerase (RdRp) 1. Thus, the non-structural protein 12 (nsp12) RdRp of the human coronavirus represents an attractive target to develop a possible therapeutic agent. Sofosbuvir proved itself as a potential anti-SARS-CoV-2 RdRp and could inhibit viral replication and infection propagation.
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New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new... more
New SARS-CoV-2 variants emerged in the United Kingdom and South Africa in December 2020 in concomitant with the Brazillian variant in February 2021 (B.1.1.248 lineage) and currently sparking worldwide during the last few months. The new strain 501.V2 in South Africa bears three mutations in the spike receptor-binding domain (RBD); K417 N, E484K, and N501Y, while the Brazilian B.1.1.248 lineage has 12 mutations. In the current study, we simulate the complex ACE2-SARS-CoV-2 spike RBD system in which the RBD is in the wild-type and mutated isoforms. Additionally, the cell-surface Glucose Regulated Protein 78 (CS-GRP78) associated with the ACE2-SARS-CoV-2 spike RBD complex (ACE2-S RBD) is modeled at the presence of these mutant variants of the viral spike. The results showed that E484K and N501Y are critical in viral spike recognition through either ACE2 or CS-GRP78. The mutated variants (the UK, South African, and Brazilian) of the spike RBD tightly bind to GRP78 more than in the case of the wild-type RBD. These results point to the potent role of GRP78 with ACE2 in the attachment of the new variants, which could be a key for the design of inhibitors to block SARS-CoV-2 attachment and entry to the host cell.
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Hepatitis C Virus (HCV) is the main causative factor for liver cirrhosis and the development of liver cancer, with a confirmed ~ 180 million infections worldwide. E2 is an HCV structural protein responsible for virus entry to the host... more
Hepatitis C Virus (HCV) is the main causative factor for liver cirrhosis and the development of liver cancer, with a confirmed ~ 180 million infections worldwide. E2 is an HCV structural protein responsible for virus entry to the host cell. Heat Shock Protein A5 (HSPA5), also termed BiP and GRP78, is the master regulator of the unfolded protein response mechanism, where it mainly localizes in the lumen of the Endoplasmic Reticulum (ER) in normal conditions. Under the stress of HCV infection or carcinogenesis, HSPA5 is upregulated. Consequently, HSPA5 escapes the ER retention localization and translocates to the cytoplasm and plasma membrane. Pep42, a cyclic peptide that was reported to target explicitly cell-surface HSPA5 in vivo. Owing to the high sequence and structural conservation between the C554-C566 region of HCV E2 and the Pep42, then we propose that the HCV E2 C554-C566 region could be the recognition site. The motivation of this work is to predict the possible binding mode...
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Aim: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) and COVID-19 cause severe acute, deadly, pneumonia. Papain-like protease (PLpro), is HCoV cysteine protease encoded within the Non-Structural protein 3. Materials and... more
Aim: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) and COVID-19 cause severe acute, deadly, pneumonia. Papain-like protease (PLpro), is HCoV cysteine protease encoded within the Non-Structural protein 3. Materials and Methods: Molecular docking is performed to test the binding performance of six protease inhibitors against MERS CoV and SARS-CoV-2 PLpro. Results: The compound, GRL-0667, shows the highest binding affinity to MERS CoV PLpro, while Grazoprevir shows the highest binding affinity against HCV NS3. Moreover, the interaction pattern in the case of HCV NS3 is the same as in the case of coronaviruses. Conclusion: The present study shows the ability of some anti-SARS CoV and anti-HCV NS3 drugs to inhibit MERS CoV PLpro, interestingly, including the newly emerged SARS-COV-2 PLpro.
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A new mysterious coronavirus outbreak started last month in China. The World Health Organization (WHO) termed the new virus strain 2019-nCoV to be the seventh reported human coronaviruses (HCoV). A seafood market in Wuhan city, central... more
A new mysterious coronavirus outbreak started last month in China. The World Health Organization (WHO) termed the new virus strain 2019-nCoV to be the seventh reported human coronaviruses (HCoV). A seafood market in Wuhan city, central China was the starting point of the emergence with unknown animal causes the first animal to human infection. Until today 904 confirmed deaths and more than 40000 cases confirmed in China and 28 countries. There is a massive fear of the human to human transmission of 2019-nCoV that reported last week by the Chinese government. The most famous two strains of HCoV are the Severe Acute Respiratory Syndrome coronavirus (SARS CoV) and the Middle East Respiratory Syndrome coronavirus (MERS CoV). The former had emerged in China in 2002 while the latter emerged in the Middle East region in 2012 and south Korea in 2015. In this study, the newly emerged 2019-nCoV papain-like protease (PLpro) is targeted by anti-SARS PLpro drugs and the anti-Hepatitis C Virus (H...
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Aim: During the last 2 years, the zika virus (ZIKV) outbreak has rapidly spread worldwide to more than 80 countries. In the last decade, nucleotide inhibitors (NIs) have been widely studied against different viruses such as HCV and human... more
Aim: During the last 2 years, the zika virus (ZIKV) outbreak has rapidly spread worldwide to more than 80 countries. In the last decade, nucleotide inhibitors (NIs) have been widely studied against different viruses such as HCV and human coronaviruses. Materials & methods: In this study, four novel guanosine derivatives were tested in silico against ZIKV polymerase. Discussion: The modified guanosines at position 2′ in the ribose ring gave comparable binding energies to that of GTP; hence, it could compete with GTP for the ZIKV polymerase active site and halt viral replication. Conclusion: The suggested guanosine derivatives had a higher affinity than ribavirin (wide range antiviral drug) in binding to ZIKV polymerase.
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Research Interests: Pharmacology, Biochemistry, Biophysics, Mental Health, Biotechnology, and 14 moreCancer, Biology, Virology, Infectious Diseases, Space Science, RNA polymerase, Medicine, Biological Sciences, Environmental Sciences, Molecular docking, CHEMICAL SCIENCES, Drug-Protein Interaction, RNA Dependent RNA Polymerase, and Zika Virus
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Aim: IDX-184 is a nonstructural 5b nucleoside inhibitor (NI) that was under clinical trials against HCV. This work adopts a molecular modeling approach in order to study the interaction between IDX-184 and HCV polymerase from four... more
Aim: IDX-184 is a nonstructural 5b nucleoside inhibitor (NI) that was under clinical trials against HCV. This work adopts a molecular modeling approach in order to study the interaction between IDX-184 and HCV polymerase from four different genotypes. Methods: Comparisons to the native nucleotide (Guanosine triphosphate) and other NIs were performed using interaction descriptors, calculated using semiempirical quantum mechanics and molecular docking. Results: IDX-184 shows potent binding to the active site of the polymerases. In addition, IDX-184 was better than Sofosbuvir and Ribavirin when docked into polymerase active site (even with experimentally solved structure). Conclusion: Analysis of the interaction descriptors and docking complexes suggests IDX-184 as a superior NI against the studied HCV subtypes.
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Research Interests: Microbiology, Clinical Trial, Medical Microbiology, Biology, Virology, and 15 moreDrug Discovery, Enzyme Inhibitors, Medicine, Hepatitis C, Humans, Computer Simulation, Hepatitis C Virus, Molecular docking, Medical virology, Protein Modeling, Outbreak, Antiviral Agents, Zika Virus, Clinical Trials as Topic, and Hepacivirus
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The current available treatment for hepatitis C virus (HCV)-the causative of liver cirrhosis and development of liver cancer-is a dual therapy using modified interferon and ribavirin. While this regimen increases the sustained viral... more
The current available treatment for hepatitis C virus (HCV)-the causative of liver cirrhosis and development of liver cancer-is a dual therapy using modified interferon and ribavirin. While this regimen increases the sustained viral response rate up to 40-80 % in different genotypes, unfortunately, it is poorly tolerated by patients. PSI-7977, a prodrug for PSI-7409, is a Non-Structural 5b (NS5b) polymerase nucleoside inhibitor that is currently in phase III clinical trials. The activated PSI-7977 is a direct acting antiviral (DAA) drug that acts on NS5b polymerase of HCV through a coordination bond with the two Mg(+2) present at the GDD active site motif. The present work utilizes a molecular modeling approach for studying the interaction between the activated PSI-7977 and the 12 amino acids constituting a 5 Å region surrounding the GDD active triad motif for HCV genotypes 1a, 2b, 3b and 4a. The analysis of the interaction parameters suggests that PSI-7977 is probably a better DAA drug for HCV genotypes 1a and 3b rather than genotypes 2b and 4a.
Research Interests: Bioinformatics, Molecular Biology, Computational Biology, Biology, Virology, and 15 moreProtein, Enzyme Inhibitors, Medicine, Hepatitis C, Humans, Sequence alignment, Hepatitis C Virus, Prodrug, Genotype, Amino Acid Sequence, Ribavirin, Antiviral Agents, Biochemistry and cell biology, Molecular Sequence Data, and Hepacivirus
ABSTRACT This work investigates the possibility of improving the biological activity of Telaprevir; an HCV NS3 protease inhibitor. This is carried out through the suggestion of 11 modified compounds of Telaprevir and calculating their... more
ABSTRACT This work investigates the possibility of improving the biological activity of Telaprevir; an HCV NS3 protease inhibitor. This is carried out through the suggestion of 11 modified compounds of Telaprevir and calculating their electronic and Quantitative Structure Activity Relationship (QSAR) parameters using molecular modeling via PM3 method. Results show that the compound number 6 (with 1,3- dithiolane ring at position R2) has more favorable electronic and QSAR parameters compared to Telaprevir. Therefore, this modified compound would be considered as a promising novel HVC NS3 protease inhibitor.
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Background: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory... more
Background: The lack of anti-COVID-19 treatment to date warrants urgent research into potential therapeutic targets. Virtual drug screening techniques enable the identification of novel compounds that target the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Main Protease (Mpro). Objective: The binding of the halogenated compounds to Mpro may inhibit the replication and transcription of SARS-CoV-2 and, ultimately, stop the viral life cycle. In times of dire need for anti- COVID-19 treatment, this study lays the groundwork for further experimental research to investigate these compounds' efficacy and potential medical uses to treat COVID-19. Method: New heterocyclic compounds were synthesized through the first reaction of cyclohexane- 1, 3-dione (1a) or dimedone (1b) with trichloroacetonitrile (2) to give the 2,2,2-trichloroethylidene) cyclohexane-1,3-dione derivatives 3a and 3b, respectively. The latter compounds underwent a series of heterocyclization reactions to...
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According to the World Health Organization (WHO), SARS-CoV-2 is responsible for more than 5 M deaths and is reported in 223 countries infecting +250 M people.
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Mucormycosis is a severe fungal infection reported in many cancer survivors, diabetic and immune-suppressed patients during organ transplants. A vast spark in the reported COVID-19 cases is noticed in India during the second wave in May... more
Mucormycosis is a severe fungal infection reported in many cancer survivors, diabetic and immune-suppressed patients during organ transplants. A vast spark in the reported COVID-19 cases is noticed in India during the second wave in May 2021, when Mucormycosis is declared an epidemic. Despite being a rare disease, the mortality rate associated with Mucormycosis is more than 40%. Spore coat proteins (CotH) are essential proteins in many pathogenic bacteria and fungi. CotH3 was reported as the vital protein required for fungal virulence in Mucormycosis. We previously reported the involvement of the host cell-surface receptor GRP78 in SARS-CoV-2 spike recognition. Additionally, GRP78 is known to be the virulence factor during Mucormycosis. Using state-of-the-art structural bioinformatics and molecular modeling tools, we predicted the GRP78 binding site to the Rhizopus delemar CotH3 protein. Our findings pave the way toward rationally designing small molecule inhibitors targeting the GR...
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Software and Techniques for Bio-Molecular Modelling | www.austinpublishinggroup.com/ebooks Copyright Elfiky AA. This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows... more
Software and Techniques for Bio-Molecular Modelling | www.austinpublishinggroup.com/ebooks Copyright Elfiky AA. This book chapter is open access distributed under the Creative Commons Attribution 4.0 International License, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited. Elfiky AA*1,2, Gawad WA1 and Elshemey WM1 1Biophysics Department, Faculty of Science, CairoUniversity, Egypt 2Biochemistry and Structural Biology Department, Center of Molecular Protein Science CMPS, Lund University, Sweden *Corresponding author: Elfiky AA, Biochemistry and Structural Biology Department, Center of Molecular Protein Science CMPS, Lund University, Sweden, Tel: +201115121528; Fax: +46736478322; Email: abdo@sci.cu.edu.eg, abdo.mohamed@biochemistry.lu.se
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Myocardial perfusion imaging (MPI) is widely used as standard of care in patients with coronary artery disease. The availability of hybrid SPECT/CT imaging system and associated advanced reconstruction algorithms serve to improve... more
Myocardial perfusion imaging (MPI) is widely used as standard of care in patients with coronary artery disease. The availability of hybrid SPECT/CT imaging system and associated advanced reconstruction algorithms serve to improve diagnostic accuracy and enhances image quality of MPI. The aim of this work was to evaluate the relative performance of iterative reconstruction algorithms correcting for different combinations of image degrading factors versus filtered back projection on the quality of myocardial perfusion SPECT imaging. A standard cardiac phantom containing myocardial defects of different sizes and compositions was used to simulate myocardial perfusion SPECT/CT clinical studies. A clinically relevant activity was determined to avoid discordance with real data acquisition. Acquisition parameters including time per projection, angular rotation increment, and iterative reconstruction number of iterations and subsets were varied. The reconstruction was carried out applying di...
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The current pandemic of the coronavirus disease-2019 (COVID-19) has badly affected our life during the year 2020. SARS-CoV-2 is the primary causative agent of the newly emerged pandemic. Natural flavonoids, Terpenoid and Thymoquinone are... more
The current pandemic of the coronavirus disease-2019 (COVID-19) has badly affected our life during the year 2020. SARS-CoV-2 is the primary causative agent of the newly emerged pandemic. Natural flavonoids, Terpenoid and Thymoquinone are tested against different viral and host-cell protein targets. These natural compounds have a good history in treating Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV). Molecular docking combined with cytotoxicity and plaque reduction assay is used to test the natural compounds against different viral (Spike, RdRp, and Mpro) and host-cell (TMPRSS II, keap 1, and ACE2) targets. The results demonstrate the binding possibility of the natural compounds (Thymol, Carvacrol, Hesperidine, and Thymoquinone) to the viral main protease (Mpro). Some of these natural compounds were approved to start clinical trail from Egypt Center for Research and Regenerative Medicine ECRRM IRB (Certificate No.IRB00012517)
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A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome... more
A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible indivi...
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New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H,... more
New SARS-CoV-2 variant VUI 202012/01 started in the UK and currently spreading in Europe and Australia during the last few days. The new variant bears about nine mutations in the spike protein (Δ69-70, Δ145, N501Y, A570D, D614G, P681H, T716I, S982A, and D1118H). The N501Y lies in the receptor-binding domain (RBD) of the spike and interacts with the host-cell receptor ACE2 responsible for viral recognition and entry. We tried to simulate the system of ACE2-SARS-CoV-2 spike RBD in the wildtype and mutated isoform of the RBD (N501Y). Additionally, the GRP78 association with the ACE2-SARS-CoV-2 spike RBD is modeled at the presence of this mutant variant of the viral spike.
In the last decade, several studies have reported that Wide-Angle X-ray Scattering (WAXS) from protein in solution contains valuable information about protein secondary and tertiary structures. Nevertheless, the use of such information... more
In the last decade, several studies have reported that Wide-Angle X-ray Scattering (WAXS) from protein in solution contains valuable information about protein secondary and tertiary structures. Nevertheless, the use of such information will remain limited until a clear understanding of the correlation between protein structural elements and WAXS profile regions is established. In this work, large number of possible protein
Research Interests: Bioinformatics, Computational Biology, Small angle X-ray and neutron scattering, Protein, Small Angle X Ray Scattering, and 15 moreModel validation, Model Selection, Mathematical Computing, Wide Angle X-Ray Scattering, Protein structure, Proteins, Protein Secondary Structure Prediction, X ray diffraction, Solutions, Comparative modeling, Reproducibility of Results, Protein Conformation, Protein Modeling, Biochemistry and cell biology, and Experimental Model
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The newly emerged human coronavirus, SARS-CoV-2, had begun to spread last year and sparked worldwide. In this study, molecular docking is utilized to test some previously approved drugs against the SARS-CoV-2 nonstructural protein 15... more
The newly emerged human coronavirus, SARS-CoV-2, had begun to spread last year and sparked worldwide. In this study, molecular docking is utilized to test some previously approved drugs against the SARS-CoV-2 nonstructural protein 15 (Nsp15). We screened 23 drugs, from which three (saquinavir, valrubicin and aprepitant) show a paramount predicted binding affinity (-9.1, -9.6 and -9.2 kcal/mol, respectively) against SARS-CoV-2 Nsp15. Moreover, saquinavir and aprepitant make nonbonded interactions with Leu201 in the active site cavity of Nsp15, while the drug valrubicin interacts with Arg199 and Leu201. This binding pattern may be effective against the targeted protein, leading to Nsp15 blockage and virus abolition. Additionally, the pharmacological properties of the screened drugs are known since they have been approved against different viruses.
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An in-house library of 173 phytocompound structures from Vernonia amygdalina and Occinum gratissimum was screened against the active region of 3-Chymotrypsin-Like Protease (3CLpro) of SARS-CoV-2 in silico. Based on docking scores and... more
An in-house library of 173 phytocompound structures from Vernonia amygdalina and Occinum gratissimum was screened against the active region of 3-Chymotrypsin-Like Protease (3CLpro) of SARS-CoV-2 in silico. Based on docking scores and reference inhibitors, a hit- list of 21 phytocompounds, with binding energies ranging from − 7.2 to -8.0 kcal/mol, was initially generated. Further docking against the 3CLpro of related coronaviruses (SARS-CoV and MERSCoV), docking to 5 different representative conformations generated from the cluster analysis of SARS-CoV-2 3CLpro molecular dynamics simulation (MDS) trajectories, and in silico drug-likeness analyses, revealed two drug-like terpenoid structures as promising non-covalent inhibitors of SARS-CoV-2 3CLPro viz: neoandrographolide and vernolide. These terpenoid structures are accommodated within the substrate-binding pocket, and interacted with the catalytic dyad, the oxyanion loop (residues 138–145), and the S1/S2 subsites of the enzyme active site. With the aid of an array of hydrogen bonds and hydrophobic interactions with residues 142–145, these phytocompounds may stabilize the conformation of the §exible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during proteolytic cleavage. Molecular dynamics simulation and binding free energy calculation further revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability, which could be adapted for experimental models.
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The human coronavirus (HCoV), SARS-CoV-2, caused more than 34 M confirmed infections from which more than 1 M deaths are reported until now (the WHO situation report-154). The current pandemic causes severe socio-economic burden. Due to... more
The human coronavirus (HCoV), SARS-CoV-2, caused more than 34 M confirmed infections from which more than 1 M deaths are reported until now (the WHO situation report-154). The current pandemic causes severe socio-economic burden. Due to the importance of understanding of the mode of recognition and viral entry, spike protein shed drug designers as the first look protein target with the first released solved structure on 26 February 2020 (PDB ID: 6VSB). It is proposed that the recognition site for GRP78 is found in SARS-CoV-2 and the immersed human coronaviruses but experimental validation is still required.
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Corona Virus Disease 2019 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Exploiting the potentials of phytocompounds is an integral component of the international response to this... more
Corona Virus Disease 2019 (COVID-19) is a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Exploiting the potentials of phytocompounds is an integral component of the international response to this pandemic. In this study, a virtual screening through molecular docking analysis was used to screen a total of 226 bioactive compounds from African herbs and medicinal plants for direct interactions with SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). From these, 36 phytocompounds with binding affinities higher than the approved reference drugs (remdesivir and sobosivir), were further docked targeting the active sites of SARS-CoV-2, as well as SARS-CoV and HCV RdRp. A hit list of 7 compounds alongside two positive controls (remdesivir and sofosbuvir) and two negative controls (cinnamaldehyde and Thymoquinone) were further docked into the active site of 8 different conformations of SARS-CoV-2 RdRp gotten from molecular dynamics simulation (MDS) system equilib...
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Mucormycosis has been reported in many regions associated with SARS-CoV-2 infections during the past few months. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target in viral and fungal pathogens. Molecular docking... more
Mucormycosis has been reported in many regions associated with SARS-CoV-2 infections during the past few months. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target in viral and fungal pathogens. Molecular docking combined with molecular dynamics simulation (MDS) is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. Additionally, the human Inosine monophosphate dehydrogenase (IMPDH) was targeted by the same inhibitors. The results reveal a comparable binding affinity of four nucleotide derivatives compared to remdesivir and sofosbuvir against both IMPDH and the RdRps of SARS-CoV-2 and Rhizopus oryzae, the main causing agent of mucormycosis. The binding affinities are calculated using different conformations of the RdRps after 100 ns MDS and trajectories clustering. The present study suggests the triple inhibition potential of four nucleotide inhibitors against SARS-CoV-2 ...
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A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or... more
A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (−8.1 ± 0.33 kcal/mol, −8.0 ± 0.35 kcal/mol, and −8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (−6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.