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  1. Article ; Online: Making COVID-19 mRNA vaccines accessible: challenges resolved.

    Niazi, Sarfaraz K

    Expert review of vaccines

    2022  Volume 21, Issue 9, Page(s) 1163–1176

    Abstract: Introduction: The rapid spread of SARS-CoV2 infection allowed testing of mRNA vaccines ...

    Abstract Introduction: The rapid spread of SARS-CoV2 infection allowed testing of mRNA vaccines that translate the target antigen, unlike introducing antigens in traditional vaccines. It proved safer and more effective and, as a chemical vaccine, much easier to develop and manufacture.
    Areas covered: The science and technology behind the mRNA vaccines are pertinent to establishing low-cost manufacturing of reverse-engineered mRNA vaccines, as suggested by the WHO. A stepwise approach to establishing a compliant manufacturing facility, testing, supply chain, regulatory submissions, and intellectual property handling is presented.
    Expert opinion: mRNA technology is more straightforward, and the cost of establishing a manufacturing facility is affordable, even in developing countries. The technology and supplies are widely available; however, based on experience, several misconceptions and misunderstandings about mRNA vaccines need to be removed, such as the regulatory and intellectual property issues that are resolved in this paper.
    MeSH term(s) COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; RNA, Viral ; SARS-CoV-2/genetics ; Vaccines ; Vaccines, Synthetic ; mRNA Vaccines
    Chemical Substances COVID-19 Vaccines ; RNA, Viral ; Vaccines ; Vaccines, Synthetic ; mRNA Vaccines
    Language English
    Publishing date 2022-06-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 2181284-6
    ISSN 1744-8395 ; 1476-0584
    ISSN (online) 1744-8395
    ISSN 1476-0584
    DOI 10.1080/14760584.2022.2089121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Combining fragment docking with graph theory to improve ligand docking for homology model structures.

    Sarfaraz, Sara / Muneer, Iqra / Liu, Haiyan

    Journal of computer-aided molecular design

    2020  Volume 34, Issue 12, Page(s) 1237–1259

    Abstract: ... recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease. For all complexes, poses ...

    Abstract Computational protein-ligand docking is well-known to be prone to inaccuracies in input receptor structures, and it is challenging to obtain good docking results with computationally predicted receptor structures (e.g. through homology modeling). Here we introduce a fragment-based docking method and test if it reduces requirements on the accuracy of an input receptor structures relative to non-fragment docking approaches. In this method, small rigid fragments are docked first using AutoDock Vina to generate a large number of favorably docked poses spanning the receptor binding pocket. Then a graph theory maximum clique algorithm is applied to find combined sets of docked poses of different fragment types onto which the complete ligand can be properly aligned. On the basis of these alignments, possible binding poses of complete ligand are determined. This docking method is first tested for bound docking on a series of Cytochrome P450 (CYP450) enzyme-substrate complexes, in which experimentally determined receptor structures are used. For all complexes tested, ligand poses of less than 1 Å root mean square deviations (RMSD) from the actual binding positions can be recovered. Then the method is tested for unbound docking with modeled receptor structures for a number of protein-ligand complexes from different families including the very recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease. For all complexes, poses with RMSD less than 3 Å from actual binding positions can be recovered. Our results suggest that for docking with approximately modeled receptor structures, fragment-based methods can be more effective than common complete ligand docking approaches.
    MeSH term(s) ATPases Associated with Diverse Cellular Activities/chemistry ; ATPases Associated with Diverse Cellular Activities/metabolism ; Betacoronavirus/enzymology ; COVID-19 ; Coronavirus 3C Proteases ; Coronavirus Infections/drug therapy ; Cysteine Endopeptidases/chemistry ; Cysteine Endopeptidases/drug effects ; Cysteine Endopeptidases/metabolism ; Cytochrome P-450 Enzyme System/chemistry ; Cytochrome P-450 Enzyme System/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Humans ; Ligands ; Models, Chemical ; Models, Molecular ; Molecular Chaperones/chemistry ; Molecular Chaperones/metabolism ; Molecular Docking Simulation ; Pandemics ; Peptide Fragments/chemistry ; Peptide Fragments/metabolism ; Pneumonia, Viral/drug therapy ; Protein Binding ; Protein Conformation ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/metabolism ; SARS-CoV-2 ; Transcription Factors/chemistry ; Transcription Factors/metabolism ; Viral Nonstructural Proteins/chemistry ; Viral Nonstructural Proteins/drug effects ; Viral Nonstructural Proteins/metabolism
    Chemical Substances BRD2 protein, human ; DNA-Binding Proteins ; Ligands ; Molecular Chaperones ; Peptide Fragments ; Receptors, G-Protein-Coupled ; Transcription Factors ; Viral Nonstructural Proteins ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cysteine Endopeptidases (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; ATAD2 protein, human (EC 3.6.1.3) ; ATPases Associated with Diverse Cellular Activities (EC 3.6.4.-)
    Keywords covid19
    Language English
    Publishing date 2020-10-09
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 808166-9
    ISSN 1573-4951 ; 0920-654X
    ISSN (online) 1573-4951
    ISSN 0920-654X
    DOI 10.1007/s10822-020-00345-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Effect of Remdesivir on mortality and length of stay in hospitalized COVID-19 patients: A single center study.

    Shaikh, Quratulain / Sarfaraz, Samreen / Rahim, Anum / Hussain, Mujahid / Shah, Rabeea / Soomro, Sara

    Pakistan journal of medical sciences

    2022  Volume 38, Issue 2, Page(s) 405–410

    Abstract: Objectives: To see the difference in mortality among hospitalized COVID-19 patients given Remdesivir (RDV) with those who were not given RDV.: Methods: A prospective cohort study was conducted on patients who were admitted to the COVID-19 isolation ... ...

    Abstract Objectives: To see the difference in mortality among hospitalized COVID-19 patients given Remdesivir (RDV) with those who were not given RDV.
    Methods: A prospective cohort study was conducted on patients who were admitted to the COVID-19 isolation unit at The Indus Hospital, Korangi Campus Karachi between March and June 2020.
    Results: Groups were similar in age and gender distribution. RDV group was more hypoxic, had severe ARDS and needed higher Oxygen support compared to non-RDV group (p=0.000). Median SOFA score was 2 in RDV vs 5 in non-RDV (p=0.000). More than moderate COVID pneumonia was found in 92% of the RDV group while 89% of non-RDV group (p value=0.001). Median day of illness to administer Remdesivir was 10. There was no difference in mortality (45.5% in RDV vs 40.4% in non-RDV; p=0.4) between the two groups. Median length of hospital stay was 12 days (IQR=7.5-14.5) in RDV group compared to 10 days (IQR=6-14) in non-RDV group (p=0.009).
    Conclusion: RDV did not show any difference in in-hospital mortality in our patients. More patients had severe ARDS in the RDV group while patients in the non-RDV group had higher SOFA score and multi-organ failure. Length of stay was longer in patients receiving Remdesivir.
    Language English
    Publishing date 2022-03-16
    Publishing country Pakistan
    Document type Journal Article
    ZDB-ID 2032827-8
    ISSN 1681-715X ; 1682-024X ; 1017-4699
    ISSN (online) 1681-715X
    ISSN 1682-024X ; 1017-4699
    DOI 10.12669/pjms.38.ICON-2022.5779
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Repurposing FIASMAs against Acid Sphingomyelinase for COVID-19: A Computational Molecular Docking and Dynamic Simulation Approach.

    Naz, Aliza / Asif, Sumbul / Alwutayd, Khairiah Mubarak / Sarfaraz, Sara / Abbasi, Sumra Wajid / Abbasi, Asim / Alenazi, Abdulkareem M / Hasan, Mohamed E

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 7

    Abstract: ... Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway ... activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional ... inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 ...

    Abstract Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit acid sphingomyelinase activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 into the cells. To achieve our objective, a drug library containing 257 functional inhibitors of ASM was constructed. Computational molecular docking was applied to dock the library against the target protein (PDB: 5I81). The potential binding site of the target protein was identified through structural alignment with the known binding pocket of a protein with a similar function. AutoDock Vina was used to carry out the docking steps. The docking results were analyzed and the inhibitors were screened based on their binding affinity scores and ADME properties. Among the 257 functional inhibitors, Dutasteride, Cepharanthine, and Zafirlukast presented the lowest binding affinity scores of -9.7, -9.6, and -9.5 kcal/mol, respectively. Furthermore, computational ADME analysis of these results revealed Cepharanthine and Zafirlukast to have non-toxic properties. To further validate these findings, the top two inhibitors in complex with the target protein were subjected to molecular dynamic simulations at 100 ns. The molecular interactions and stability of these compounds revealed that these inhibitors could be a promising tool for inhibiting SARS-CoV-2 infection.
    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2 ; Molecular Docking Simulation ; Drug Repositioning ; Sphingomyelin Phosphodiesterase ; Protease Inhibitors/chemistry ; Molecular Dynamics Simulation ; Antiviral Agents/pharmacology
    Chemical Substances zafirlukast (XZ629S5L50) ; Sphingomyelin Phosphodiesterase (EC 3.1.4.12) ; Protease Inhibitors ; Antiviral Agents
    Language English
    Publishing date 2023-03-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28072989
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Application of Data Mining Algorithm to Investigate the Effect of Intelligent Transportation Systems on Road Accidents Reduction by Decision Tree

    Mohammad Mehdi Khabiri / Fatemeh Matin Ghahfarokhi / Sara Sarfaraz / Hasan Mohammadi Anaie

    Communications, Vol 24, Iss 2, Pp F36-F

    2022  Volume 45

    Abstract: Due to the large amount of available data in this study, authors have utilized data mining algorithms, especially the decision tree, to process these data and obtain the information, which would result in increasing road safety, determining the causes ... ...

    Abstract Due to the large amount of available data in this study, authors have utilized data mining algorithms, especially the decision tree, to process these data and obtain the information, which would result in increasing road safety, determining the causes affecting it and patterns leading to traffic accidents. The effective use of this tool and its role in controlling the number of driving accidents is the subject of this study with the help of data mining algorithms. The results show that the increase in the number of roadside assistances to more than 41; number of driving accidents (fatally injured) is not significantly different, hence one of the proposed strategies for intelligent relay stations and its organization with the intelligent transportation tool is available. The intelligent transportation system utilities comprise of monitoring, guidance and enforcement tools, plus service tools such as rescue, driver assistant and road improvement.
    Keywords data mining algorithm ; intelligent transportation systems (its) ; driving accidents ; road safety ; decision tree ; Transportation and communications ; HE1-9990 ; Science ; Q ; Transportation engineering ; TA1001-1280
    Subject code 380
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher University of Žilina
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Repurposing FIASMAs against Acid Sphingomyelinase for COVID-19

    Aliza Naz / Sumbul Asif / Khairiah Mubarak Alwutayd / Sara Sarfaraz / Sumra Wajid Abbasi / Asim Abbasi / Abdulkareem M. Alenazi / Mohamed E. Hasan

    Molecules, Vol 28, Iss 2989, p

    A Computational Molecular Docking and Dynamic Simulation Approach

    2023  Volume 2989

    Abstract: ... Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway ... activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional ... inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 ...

    Abstract Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit acid sphingomyelinase activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 into the cells. To achieve our objective, a drug library containing 257 functional inhibitors of ASM was constructed. Computational molecular docking was applied to dock the library against the target protein (PDB: 5I81). The potential binding site of the target protein was identified through structural alignment with the known binding pocket of a protein with a similar function. AutoDock Vina was used to carry out the docking steps. The docking results were analyzed and the inhibitors were screened based on their binding affinity scores and ADME properties. Among the 257 functional inhibitors, Dutasteride, Cepharanthine, and Zafirlukast presented the lowest binding affinity scores of −9.7, −9.6, and −9.5 kcal/mol, respectively. Furthermore, computational ADME analysis of these results revealed Cepharanthine and Zafirlukast to have non-toxic properties. To further validate these findings, the top two inhibitors in complex with the target protein were subjected to molecular dynamic simulations at 100 ns. The molecular interactions and stability of these compounds revealed that these inhibitors could be a promising tool for inhibiting SARS-CoV-2 infection.
    Keywords SARS-CoV-2 ; acid sphingomyelinase (ASM) ; functional inhibitors ; molecular docking ; molecular dynamics ; COVID-19 ; Organic chemistry ; QD241-441
    Subject code 540 ; 500
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Recent Advances in Machine-Learning-Based Chemoinformatics: A Comprehensive Review.

    Niazi, Sarfaraz K / Mariam, Zamara

    International journal of molecular sciences

    2023  Volume 24, Issue 14

    Abstract: ... with the structure-activity relationships (SARs), are pivotal in unlocking the pathway to small-molecule drug discovery. Technical ...

    Abstract In modern drug discovery, the combination of chemoinformatics and quantitative structure-activity relationship (QSAR) modeling has emerged as a formidable alliance, enabling researchers to harness the vast potential of machine learning (ML) techniques for predictive molecular design and analysis. This review delves into the fundamental aspects of chemoinformatics, elucidating the intricate nature of chemical data and the crucial role of molecular descriptors in unveiling the underlying molecular properties. Molecular descriptors, including 2D fingerprints and topological indices, in conjunction with the structure-activity relationships (SARs), are pivotal in unlocking the pathway to small-molecule drug discovery. Technical intricacies of developing robust ML-QSAR models, including feature selection, model validation, and performance evaluation, are discussed herewith. Various ML algorithms, such as regression analysis and support vector machines, are showcased in the text for their ability to predict and comprehend the relationships between molecular structures and biological activities. This review serves as a comprehensive guide for researchers, providing an understanding of the synergy between chemoinformatics, QSAR, and ML. Due to embracing these cutting-edge technologies, predictive molecular analysis holds promise for expediting the discovery of novel therapeutic agents in the pharmaceutical sciences.
    MeSH term(s) Cheminformatics ; Drug Discovery/methods ; Machine Learning ; Algorithms ; Molecular Structure ; Quantitative Structure-Activity Relationship
    Language English
    Publishing date 2023-07-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241411488
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Combining fragment docking with graph theory to improve ligand docking for homology model structures

    Sarfaraz, Sara / Muneer, Iqra / Liu, Haiyan

    J Comput Aided Mol Des

    Abstract: ... recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease. For all complexes, poses ...

    Abstract Computational protein-ligand docking is well-known to be prone to inaccuracies in input receptor structures, and it is challenging to obtain good docking results with computationally predicted receptor structures (e.g. through homology modeling). Here we introduce a fragment-based docking method and test if it reduces requirements on the accuracy of an input receptor structures relative to non-fragment docking approaches. In this method, small rigid fragments are docked first using AutoDock Vina to generate a large number of favorably docked poses spanning the receptor binding pocket. Then a graph theory maximum clique algorithm is applied to find combined sets of docked poses of different fragment types onto which the complete ligand can be properly aligned. On the basis of these alignments, possible binding poses of complete ligand are determined. This docking method is first tested for bound docking on a series of Cytochrome P450 (CYP450) enzyme-substrate complexes, in which experimentally determined receptor structures are used. For all complexes tested, ligand poses of less than 1 Å root mean square deviations (RMSD) from the actual binding positions can be recovered. Then the method is tested for unbound docking with modeled receptor structures for a number of protein-ligand complexes from different families including the very recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease. For all complexes, poses with RMSD less than 3 Å from actual binding positions can be recovered. Our results suggest that for docking with approximately modeled receptor structures, fragment-based methods can be more effective than common complete ligand docking approaches.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #841071
    Database COVID19

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  9. Article ; Online: Perylene diimide/MXene-modified graphitic pencil electrode-based electrochemical sensor for dopamine detection.

    Amara, Umay / Mehran, Muhammad Taqi / Sarfaraz, Bilal / Mahmood, Khalid / Hayat, Akhtar / Nasir, Muhammad / Riaz, Sara / Nawaz, Mian Hasnain

    Mikrochimica acta

    2021  Volume 188, Issue 7, Page(s) 230

    Abstract: The synthesis of novel architecture comprising perylene diimide (PDI)-MXene ( ... ...

    Abstract The synthesis of novel architecture comprising perylene diimide (PDI)-MXene (Ti
    MeSH term(s) Dopamine/chemistry ; Electrochemical Techniques/methods ; Electrodes/standards ; Graphite ; Humans ; Imides/chemistry ; Perylene/analogs & derivatives ; Perylene/chemistry
    Chemical Substances Imides ; perylenediimide ; Perylene (5QD5427UN7) ; Graphite (7782-42-5) ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2021-06-12
    Publishing country Austria
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 89-9
    ISSN 1436-5073 ; 0026-3672
    ISSN (online) 1436-5073
    ISSN 0026-3672
    DOI 10.1007/s00604-021-04884-0
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  10. Article: Anxiolytic and memory enhancing potential of aloe vera and flax seed oil in rats: A comparative study with valproic acid.

    Sarfaraz, Yousra / Emad, Shaista / Qadeer, Sara / Sheikh, Sheeza / Yousuf, Sarwat / Sadaf, Sana / Haider, Saida / Perveen, Tahira

    Pakistan journal of pharmaceutical sciences

    2021  Volume 33, Issue 6(Supplementary), Page(s) 2831–2836

    Abstract: For centuries, herbs and herbal oils are used for pharmacological purpose. Aloe vera is well-known as silent healer and flax seed oil is known to contain rich amount of omega-3 fatty acids, both are having effects on central nervous system. Valproic acid ...

    Abstract For centuries, herbs and herbal oils are used for pharmacological purpose. Aloe vera is well-known as silent healer and flax seed oil is known to contain rich amount of omega-3 fatty acids, both are having effects on central nervous system. Valproic acid is anticonvulsant drug with some side effects and has shown effects on behaviors. This study was designed to monitor the effects of valproic acid, aloe vera and flax seed oil on cognitive and anxiolytic behaviors in rats. Animals were categorized into four groups: Control, valproic acid, aloe vera and flax seed oil which were respectively treated with water, valproic acid (300mg/kg), aloe vera (0.4ml/kg) and flax seed oil (1.8ml/kg). The treatment was continued 2 weeks for drug and 3 weeks for aloe vera and flax seed oil. Anxiolytic effect as well as increased GABA levels were observed following drug and oil treatments. Improvement in cognitive function with decrease in acetylcholine esterase activity in aloe vera and flax seed oil while impairment in learning memory with increase acetylcholine esterase activity was observed in rats treated with valproic acid. Results showed substantial decrease in acetylcholinesterase level in aloe vera and flax seed oil supporting the cognitive impact of oils in contrary to drug.
    MeSH term(s) Aloe ; Animals ; Anti-Anxiety Agents/pharmacology ; Linseed Oil/pharmacology ; Memory/drug effects ; Rats ; Rats, Wistar ; Valproic Acid/pharmacology ; gamma-Aminobutyric Acid/analysis
    Chemical Substances Anti-Anxiety Agents ; gamma-Aminobutyric Acid (56-12-2) ; Valproic Acid (614OI1Z5WI) ; Linseed Oil (8001-26-1)
    Language English
    Publishing date 2021-04-21
    Publishing country Pakistan
    Document type Comparative Study ; Journal Article
    ZDB-ID 885131-1
    ISSN 1011-601X
    ISSN 1011-601X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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