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Mutational analysis of hepatitis E virus ORF1 'Y-domain' : Effects on RNA replication and virion infectivity

World Journal of Gastroenterology 2017年第4期23卷 590-602页

作者： mohammad khalid parvez Department of Pharmacognosy King Saud University College of PharmacyRiyadh 11451Saudi Arabia

AIMTo investigate the role of non-structural open reading frame 1 “Y-domain” sequences in the hepatitis E virus (HEV) life *** of human HEV Y-domain (amino acid sequences 216-442) and closely-related viruses were analyzed in silico. Site-directed mutagenesis of the Y-domain (HEV SAR55) was carried out and studied in the replicon-baculovirus-hepatoma cell model. In vitro transcribed mRNA (pSK-GFP) constructs were transfected into S10-3 cells and viral RNA replicating GFP-positive cells were scored by flow cytometry. Mutant virions’ infectivity was assayed on naïve HepG2/C3A *** silico analysis identified a potential palmitoylation-site (C336C337) and an α-helix segment (L410Y411S412W413L414F415E416) in the HEV Y-domain. Molecular characterization of C336A, C337A and W413A mutants of the three universally conserved residues showed non-viability. Further, of the 10 consecutive saturation mutants covering the entire Y-domain nucleotide sequences (nts 650-1339), three constructs (nts 788-994) severely affected virus replication. This revealed the indispensability of the internal sequences but not of the up- or downstream sequences at the transcriptional level. Interestingly, the three mutated residues corresponded to the downstream codons that tolerated saturation mutation, indicating their post-translational functional/structural essentiality. In addition, RNA secondary structure prediction revealed formation of stable hairpins (nts 788-994) where saturation mutation drastically inhibited virion *** is the first demonstration of the critical role of Y-domain sequences in HEV life cycle, which may involve gene regulation and/or membrane binding in intracellular replication complexes.

关键词： Hepatitis E virus Open reading frame 1 Y-domain Palmitoylation α -helix

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HBV and HIV co-infection:Impact on liver pathobiology and therapeutic approaches

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World Journal of Hepatology 2015年第1期7卷 121-126页

作者： mohammad khalid parvez Department of Pharmacognosy King Saud University College of PharmacyRiyadh 11451Saudi Arabia

The consequences of hepatitis B virus(HBV) and human immunodeficiency virus(HIV) co-infection on progression of severe liver diseases is a serious public health issue,worldwide. In the co-infection cases,about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals,liverrelated mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIVinduced liver diseases includes hepatitis,steatohepatitis,endothelialitis,necrosis,granulomatosis,cirrhosis andcarcinoma. Moreover,HIV co-infection significantly alters the natural history of hepatitis B,and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology,only a few data is available on interactions between HBV and HIV proteins. Thus,the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms,and to design effective therapeutic strategies.

关键词： Hepatitis B virus Human immunodeficiencyvirus Human immunodeficiency virus-hepatotropism Hepatitis B virus and human immunodeficiency virusco-infection Chronic hepatitis B Hepatopathogenesis

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Geometric architecture of viruses

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World Journal of Virology 2020年第2期9卷 5-18页

作者： mohammad khalid parvez Department of Pharmacognosy College of PharmacyKing Saud UniversityRiyadh 22451Saudi Arabia

In the current SARS-CoV-2 disease(COVID-19)pandemic,the structural understanding of new emerging viruses in relation to developing effective treatment and interventions are very *** present remarkable differences in geometric shapes,sizes,molecular compositions and organizations.A detailed structural knowledge of a virion is essential for understanding the mechanisms of capsid assembly/disassembly,antigenicity,cell-receptor interaction,and designing therapeutic strategies.X-ray crystallography,cryoelectron microscopy and molecular simulations have elucidated atomic-level structure of several *** view of this,a recently determined crystal structure of SARS-CoV-2 nucleocapsid has revealed its architecture and self-assembly very similar to that of the SARS-CoV-1 and the Middle-East respiratory syndrome virus(MERS-CoV).In structure determination,capsid symmetry is an important factor greatly contributing to its stability and balance between the packaged genome and *** the capsid protein subunits are asymmetrical,the maximum number of inter-subunit interactions can be established only when they are arranged ***,a stable capsid must be in a perfect symmetry and lowest possible *** virions are spherical but geometrically icosahedrons as compared to complex virions that are both isometric and *** icosahedral or helical viruses are very common in animals but rare in plants and *** capsids are defined by triangulation number(T=1,3,4,13,etc.),i.e.,the identical equilateral-triangles formed of *** significant defective capsids with or without nucleic acids are common in enveloped alpha-,flavi-and *** self-assembling,stable and non-infectious virus-like particles have been widely exploited as vaccine candidates and therapeutic molecules delivery vehicles.

关键词： Virus Virion Capsid structure Icosahedron Triangulation number

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Inhibition of hepatitis B virus DNA replicative intermediate forms by recombinant interferon-γ

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World Journal of Gastroenterology 2006年第19期12卷 3006-3014页

作者： mohammad khalid parvez Deepak Sehgal Shiv Kumar Sarin Seemi Farhat Basir Shahid Jameel Department of Biosciences Jamia Millia Islamia New DelhiVirology GroupInternational Centre for Genetic Engineering and BiotechnologyNew DelhiDepartment of GastroenterologyG.B.Pant HospitalNew DelhiIndia Virology Group International Centre for Genetic Engineering and Biotechnology New DelhiIndia Department of Gastroenterology G.B.Pant Hospital New DelhiIndia Department of Biosciences Jamia Millia Islamia New DelhiIndia

AIM: To evaluate the in vitro anti-HBV activity of recombinant human IFN-γ, alone and in combination with lamivudine. METHODS: A recombinant baculovirus-HBV/HepG2 culture system was developed which could support productive HBV infection in vitro. Expression of HBsAg and HBeAg in infected HepG2 culture medium was detected by commercial enzyme immunoassays. HBV DNA replication intermediates were detected in infected cells by Southern hybridization and viral DNA load was determined by dot hybridization. RESULTS: IFN-γat 0.1 to 5μg/L efficiently down regulated HBsAg expression in transduced HepG2 cells. At 5μg/L, IFN-γalso suppressed HBV DNA replication in these cells. While treatment with a combination of lamivudine and IFN-γshowed no additive effect, sequential treatment first with lamivudine and then IFN-γwas found to be promising. In this culture system the best HBV suppression was observed with a pulse of 2μmol/L lamivudine for two days, followed by 1μg/L IFN-γfor another four days. Compared to treatment with lamivudine alone, the sequential use of 0.2μmol/L lamivudine for two days, followed by 5μg/L IFN-γfor six days showed a 72% reduction in HBV cccDNA pool. CONCLUSION: This in vitro study warrants further evaluation of a combination of IFN-γand lamivudine, especially in IFN-αnon-responder chronic hepatitis B patients. A reduced duration of lamivudine treatment would also restrict the emergence of drug-resistant HBV mutants.

关键词： Hepatitis B virus (HBV) Lamivudine Interferon-γ Replicative intermediates cccDNA

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Driving forces of continuing evolution of rotaviruses

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World Journal of Virology 2024年第2期13卷 58-70页

作者： Mohamad Saifudin Hakim Faris Muhammad Gazali Suci Ardini Widyaningsih mohammad khalid parvez Postgraduate School of Molecular Medicine Erasmus MC-University Medical CenterRotterdam 3015GDNetherlands Viral Infection Working Group International Society of Antimicrobial ChemotherapyLondon EC4R 9ANUnited Kingdom Master Program in Biotechnology Postgraduate SchoolUniversitas Gadjah MadaYogyakarta55281Indonesia Master of Medical Sciences in Clinical Investigation Harvard Medical SchoolBostonMA 02115United States Department of Pharmacognosy College of PharmacyKing Saud UniversityRiyadh11451Saudi Arabia

Rotaviruses are non-enveloped double-stranded RNA virus that causes acute diarrheal diseases in children(<5 years).More than 90%of the global rotavirus infection in humans was caused by Rotavirus group *** infection has caused more than 200000 deaths annually and predominantly occurs in the low-income *** evolution is indicated by the strain dynamics or the emergence of the unprecedented *** major factors that drive the rotavirus evolution include the genetic shift that is caused by the reassortment mechanism,either in the intra-or the ***,other factors are also known to have an impact on rotavirus *** review discusses the structure and types,epidemiology,and evolution of *** article also reviews other supplemental factors of rotavirus evolution,such as genetic reassortment,mutation rate,glycan specificity,vaccine introduction,the host immune respo-nses,and antiviral drugs.

关键词： Rotavirus Epidemiology Evolution Reassortment Vaccine

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Decoding molecular mechanisms:brain aging and Alzheimer's disease

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Neural Regeneration Research 2025年第8期20卷 2279-2299页

作者： Mahnoor Hayat Rafay Ali Syed Hammad Qaiser mohammad Uzair khalid Al-Regaiey Roaa Khallaf Lubna Abdullah Mohammed Albassam Imdad Kaleem Xueyi Wang Ran Wang Mehwish SBhatti Shahid Bashir Atta-ur-Rahman School of Applied Biosciences(ASAB) National University of Sciences and Technology(NUST)IslamabadPakistan Department of Biotechnology Quaid-i-Azam UniversityIslamabadPakistan Department of Biological Sciences Faculty of Basic&Applied SciencesInternational Islamic University Islamabad(IIUI)IslamabadPakistan Department of Bioengineering King Fahd University of Petroleum and MineralsDhahranSaudi Arabia Department of Physiology College of MedicineKing Saud UniversityRiyadhSaudi Arabia Department of Neurology Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia Department of Mental Health Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia Department of Biosciences Commission on Science and Technology for Sustainable Development in the South(COMSATS University)IslamabadPakistan Department of Psychiatry The First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Mental Health Institute of Hebei Medical University ShijiazhuangHebei ProvinceChina Department of Neurobiology and Behavior University of CaliforniaIrvineCAUSA Neuroscience Center King Fahad Specialist Hospital DammamDammamSaudi Arabia

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for *** aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's *** these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging *** these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect *** review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

关键词： Alzheimer’s disease brain aging cognitive health dementia molecular mechanisms neuronal activity neuroplasticity neurotransmission

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Hot-pressed graphene nanoplatelets or/and zirconia reinforced hybrid alumina nanocomposites with improved toughness and mechanical characteristics

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Journal of Materials Science & Technology 2020年第5期40卷 135-145页

作者： Iftikhar Ahmad mohammad Islam Nuha Al Habis Shahid parvez Center of Excellence for Research in Engineering Materials Deanship of Scientific ResearchKing Saud UniversityP.O.Box 800Riyadh 11421Saudi Arabia Mechanical Engineering Department College of EngineeringKing Saud UniversityP.O.Box 800Riyadh 11421Saudi Arabia

This work explains the synergistic contribution of graphene nanoplatelets(GNP)and zirconia ceramic nanoparticles(ZrO2)on the microstructure,mechanical performance and ballistic properties of the alumina(Al2O3)ceramic hybrid *** the benchmarked monolithic alumina,the hotpressed hybrid nanocomposite microstructure demonstrated 68%lower grain size due to grain pinning phenomenon by the homogenously distributed reinforcing GNP(0.5 wt%)and zirconia(4 wt%)***,the hybrid nanocomposite manifested 155%better fracture toughness(KIC)and 17%higher microhardness as well as 88%superior ballistic trait over the monolithic alumina,*** superior mechanical and ballistic performance of the hybrid nanocomposites was attributed to the combined role of zirconia nanoparticles and GNP nanomaterial in refining the microstructure and inducing idiosyncratic strengthening/toughening *** combined electron microscopy revealed complicated physical interlocking of the GNP into the microstructure as well as excellent bonding of the GNP with alumina at their interface in the hybrid *** also probed the efficiency of the pull-out and crack-bridging toughening mechanisms through proven quantitative *** on the information extracted from the in-depth SEM/TEM investigation,we outlined schematic models for understating the reinforcing ability as well as toughening mechanisms in the hybrid nanocomposites and meticulously *** hot-pressed hybrid nanocomposites owning high toughness and hardness may have applications in advanced armor technology.

关键词： Graphene Alumina Zirconia Toughness Hybrid nanocomposites

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Smart Bubble Sort:A Novel and Dynamic Variant of Bubble Sort Algorithm

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Computers, Materials & Continua 2022年第6期71卷 4895-4913页

作者： mohammad khalid Imam Rahmani College of Computing and Informatics Saudi Electronic UniversityRiyadhSaudi Arabia

In the present era,a very huge volume of data is being stored in online and offline *** houses,research,medical as well as healthcare organizations,and academic institutions store data in databases and their subsequent retrievals are performed for further *** the required data from a given database within the minimum possible time is one of the key factors in achieving the best possible performance of any computer-based *** the data is already sorted,finding or searching is comparatively *** real-life scenarios,the data collected from different sources may not be in sorted *** algorithms are required to arrange the data in some order in the least possible *** this paper,I propose an intelligent approach towards designing a smart variant of the bubble sort algorithm.I call it Smart Bubble sort that exhibits dynamic footprint:The capability of adapting itself from the average-case to the best-case *** is an in-place sorting algorithm and its best-case time complexity isΩ(n).It is linear and better than bubble sort,selection sort,and merge *** averagecase and worst-case analyses,the complexity estimates are based on its static footprint *** complexity in worst-case is O(n2)and in average-case isΘ(n^(2)).Smart Bubble sort is capable of adapting itself to the best-case scenario from the average-case scenario at any subsequent stages due to its dynamic and intelligent *** Smart Bubble sort outperforms bubble sort,selection sort,and merge sort in the best-case scenario whereas it outperforms bubble sort in the average-case scenario.

关键词： Sorting algorithms smart bubble sort footprint dynamic footprint time complexity asymptotic analysis

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Demographic and socioeconomic determinants of urinary arsenic concentration for elementary school children in Bangladesh

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Global Health Journal 2024年第3期8卷 119-127页

作者： Raisa Sara khalid M.Khan Shelbin Mattathil Munachimso Nwankwo mohammad Aminul Islam Faruque parvez Department of Economics and International Business College of Business AdministrationSam Houston State UniversityHuntsvilleTX 77340USA Department of Public Health College of Health SciencesSam Houston State UniversityHuntsvilleTX 77340USA College of Osteopathic Medicine Sam Houston State UniversityConroeTX 77304USA Paul G.Allen School for Global Health Washington State UniversityPullmanWA 99164USA Department of Environmental Health Mailman School of Public HealthColumbia UniversityNew YorkNY 10032USA

Background:Arsenic(As)is a toxic element that can lead to various health issues in *** primary exposure to As is through the consumption of water contaminated with high As levels,particularly in *** studies have shown that urinary arsenic(UAs)concentration can reflect As exposure and metabolism in ***,little is known about how other factors,such as age,sex,and socioeconomic status,may affect UAs concentrations in ***:This study aimed to investigate the influence of factors such as age,sex,and socioeconomic status on UAs concentrations in children,in addition to the impact of drinking water arsenic(WAs)***:We conducted our study on elementary school-going children aged 8-11 years from rural Araihazar in *** measured UAs(available for a subset of 391 children)and WAs levels and collected information on demographic and socioeconomic *** employed regression analysis and t-tests to analyze the ***:Our findings revealed that younger children(β=197.95,95%confidence interval[CI]:111.97 to 283.94),female children(β=93.95,95%CI:8.49 to 179.40),and children with less educated fathers(β=138.03,95%CI:26.47 to 249.58)had higher UAs levels,particularly when they consumed water with high As ***:The study concludes that children's As exposure and UAs concentration may vary depending on their age,sex,and socioeconomic ***,these factors should be considered when assessing the health risks associated with As.

关键词： Waterarsenic Rural children Socioeconomicfactors Bangladesh

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Adaptive task scheduling in IoT using reinforcement learning

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International Journal of Intelligent Computing and Cybernetics 2020年第3期13卷 261-282页

作者： mohammad khalid Pandit Roohie Naaz Mir mohammad Ahsan Chishti Department of Computer Science and Engineering National Institute of Technology SrinagarSrinagarIndia

Purpose-The intelligence in the Internet of Things(IoT)can be embedded by analyzing the huge volumes of data generated by it in an ultralow latency *** computational latency incurred by the cloud-only solution can be significantly brought down by the fog computing layer,which offers a computing infrastructure to minimize the latency in service delivery and *** this purpose,a task scheduling policy based on reinforcement learning(RL)is developed that can achieve the optimal resource utilization as well as minimum time to execute tasks and significantly reduce the communication costs during distributed ***/methodology/approach-To realize this,the authors proposed a two-level neural network(NN)-based task scheduling system,where the first-level NN(feed-forward neural network/convolutional neural network[FFNN/CNN])determines whether the data stream could be analyzed(executed)in the resourceconstrained environment(edge/fog)or be directly forwarded to the *** second-level NN(RL module)schedules all the tasks sent by level 1 NN to fog layer,among the available fog *** real-time task assignment policy is used to minimize the total computational latency(makespan)as well as communication ***-Experimental results indicated that the RL technique works better than the computationally infeasible greedy approach for task scheduling and the combination of RL and task clustering algorithm reduces the communication costs ***/value-The proposed algorithm fundamentally solves the problem of task scheduling in realtime fog-based IoT with best resource utilization,minimum makespan and minimum communication cost between the tasks.

关键词： Internet of things Neural networks Task scheduling

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