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Papers by mohsin khan

Journal of Pharmaceutical Research International

Euphorbia nivulia (EN) one of the members of Euphorbiaceae family, is a medicinal plant of Cholis... more Euphorbia nivulia (EN) one of the members of Euphorbiaceae family, is a medicinal plant of Cholistan Desert (Punjab, Pakistan) that is traditionally used for a number of diseases. The plant is enriched with many phyto-constituents including flavonoids, triterpenes and polyphenols. In present study, crude extract as well as various fractions were assessed for phytochemical analysis, HPLC profiling, radical scavenging property and total phenolic and flavonoid contents. Hydro-alcoholic (70%) crude extract of EN was subjected to fractionation using different solvents including n-hexane, chloroform, butanol and aqueous. After performing the phytochemical screening and HPLC profiling, antioxidant activity was estimated by using DPPH and FRAP assays. Total flavonoid and phenolic contents were also estimated. HPLC analysis confirmed the presence of flavonoids and polyphenols like quercitin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid and ferulic a...

Coronaviruses

Background: The newly emerged delta and omicron variants of severe acute respiratory syndrome cor... more Background: The newly emerged delta and omicron variants of severe acute respiratory syndrome coronavirus (SARS-CoV-2) have affected millions of individuals globally with increased transmissible and infectivity rates. Although, numerous vaccines are available or under clinical trials to combat the SARS-CoV-2 and its variant, still, a therapeutic agent is awaited. Objective: The present work is focused on rigorous screening of chemical constituents of Azadirachta indica (A. indica) against delta and omicron variants of SARS-CoV-2 via inhibition of S-glycoprotein. Methods: Total, 10 compounds of A. indica were subjected to molecular docking and pharmacophore modeling studies against the S-glycoprotein of delta and omicron variants of SARS-CoV-2. Furthermore, homology modeling was performed for omicron S-glycoprotein with the help of SWISS-MODEL and aligned by PyMOL software. Later on, the residues of protein were verified in the allowed region via Ramachandran plot. In addition, our d...

Behavioural Neurology

E-shopping is a rapidly growing phenomenon among different individuals who intend to shop online.... more E-shopping is a rapidly growing phenomenon among different individuals who intend to shop online. However, a trust deficit in the E-shopping environment has always been a critical issue in the brick-and-click mode of shopping, being one of the main reasons for E-cart abandonment in E-commerce. This empirical study is aimed at investigating the perceived effect of website trust on E-shopping intentions and behaviour, drawing upon the theory of planned behaviour (TPB). Data were collected through self-administered questionnaires from working adults who shop for garments online. Structural equation modelling was used to evaluate the model fit and assumptions. Our findings suggest that website trust and E-shopping attitude play substantial roles in building E-shopping intentions and actual behaviours. Both are the significant predictors of the behaviour mediated by E-shopping intentions. However, E-shopping intentions did not mediate between subjective norms and E-shopping behaviour, wh...

Helsingin yliopisto, Mar 5, 2021

This thesis looks into two privacy threats of cellular networks. For their operations, these netw... more This thesis looks into two privacy threats of cellular networks. For their operations, these networks have to deal with unique permanent user identities called International Mobile Subscriber Identity (IMSI). One of the privacy threats is posed by a device called IMSI catcher. An IMSI catcher can exploit various vulnerabilities. Some of these vulnerabilities are easier to exploit than others. This thesis looks into fixing the most easily exploitable vulnerability, which is in the procedure of identifying the subscriber. This vulnerability exists in all generations of cellular networks prior to 5G. The thesis discusses solutions to fix the vulnerability in several different contexts.

Letters in Drug Design & Discovery, 2021

Background: Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic respiratory di... more Background: Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic respiratory disease with mild to severe pneumonia symptoms. No clinical antiviral agent is available so far. However, several repurposing drugs and vaccines are being given to individuals or in clinical trials against SARS-CoV-2 Objective: The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of SARS-CoV2 encoded proteins via utilizing computational tools. Method: Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic (MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO gap energy and other che...

IOP Conference Series: Materials Science and Engineering, 2020

Electromagnetic forming is a high-velocity forming process in which repulsive forces between cond... more Electromagnetic forming is a high-velocity forming process in which repulsive forces between conducting coil and workpiece are generated by mutual inductance, thus, creating opposite magnetic fields and Lorentz forces on conducting bodies. In such processes, the formability can be enhanced owing to the high-speed deformation of the material. This paper presents a fully-coupled numerical model and experimental study of the deformation behaviour of aluminium alloy (AL3014) using closed die magnetic pulse forming. The current density, magnetic flux density and Lorentz force of 1mm thick sheet were estimated numerically. The effect of deforming sheet on magnetic flux and induction was considered. As a result of which the percentage error in sheet deformation reduced from 10% for the existing uncoupled model to 5% for the fully coupled proposed model.

Journal of Biomolecular Structure and Dynamics, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coro... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-PRO ; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL-PRO-cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Ca atoms throughout the simulation run time. Interestingly, PL-PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

Journal of Biomolecular Structure and Dynamics, 2021

There is currently a dearth of specific therapies to treat respiratory infections caused by the t... more There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

Ain Shams Engineering Journal, 2021

Journal of Biomolecular Structure and Dynamics, 2021

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threate... more A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-a and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to proinflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Ca atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further.

Anti-Cancer Agents in Medicinal Chemistry, 2020

Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals ... more Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals better known as “Natural Products” are found abundantly in a number of plants. Since time immemorial, spices have been widely used in Indian cuisine as flavoring and coloring agents. Most of these spices and condiments are derived from various biodiversity hotspots in India (which contribute 75% of global spice production) and form the crux of India’s multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these spices and condiments are known to possess several medicinal properties also. Most of these spices are mentioned in the Ayurveda, the indigenous system of medicine. The antimicrobial, antioxidant, antiproliferative, antihypertensive and antidiabetic properties of several of these natural products are well documented in Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well as anti-inflammatory agents. As...

RNA (New York, N.Y.), Jun 22, 2018

Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their b... more Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their biogenesis and function is still in its infancy. It was recently shown that alternative splicing underlies the formation of circular RNAs (circRNA) arising from the Titin (TTN) gene. Since the main mechanism by which circRNAs are formed is still unclear, we hypothesized that alternative splicing, and in particular exon skipping, is a major driver of circRNA production. We performed RNA sequencing on human and mouse hearts, mapped alternative splicing events and overlaid these with expressed circRNAs at exon-level resolution. In addition, we performed RNA sequencing on hearts of Rbm20 KO mice to address how important Rbm20-mediated alternative splicing is in the production of cardiac circRNAs. In human and mouse hearts, we show that cardiac circRNAs are mostly (~90%) produced from constitutive exons and less (~10%) from alternatively spliced exons. In Rbm20 KO hearts, we identified 38 diff...

Proceedings of the National Academy of Sciences of the United States of America, Jan 19, 2017

Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells... more Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells to form central nervous system (neural plate) or sensory placodes. Grafts of different tissues into the periphery of a chicken embryo elicit different responses: Hensen's node induces a neural plate whereas the head mesoderm induces placodes. How different are these processes? Transcriptome analysis in time course reveals that both processes start by induction of a common set of genes, which later diverge. These genes are remarkably similar to those induced by an extraembryonic tissue, the hypoblast, and are normally expressed in the pregastrulation stage epiblast. Explants of this epiblast grown in the absence of further signals develop as neural plate border derivatives and eventually express lens markers. We designate this state as "preborder"; its transcriptome resembles embryonic stem cells. Finally, using sequential transplantation experiments, we show that the node,...

European Journal of Heart Failure, 2017

AimsPrevious studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for... more AimsPrevious studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF).Methods and resultsRNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)‐1306‐5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time‐points during the study's 1‐year follow‐up. The primary endpoint was the composite of all‐cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR‐1306‐5p...

JACC. Heart failure, Jul 1, 2017

In this study, the authors used biomarker profiles to characterize differences between patients w... more In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. Limited data are available on biomarker profiles in acute HFmrEF. A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with ...

European journal of heart failure, Oct 21, 2017

It is unclear whether distinct pathophysiological processes are present among patients with acute... more It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways. We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal func...

Integrative medicine research, 2017

Aromatherapy is used in clinical settings for patients suffering from several chronic and critica... more Aromatherapy is used in clinical settings for patients suffering from several chronic and critical diseases such as cancer. Ethyl acetate (EA) is a colorless liquid with a characteristic fruity smell and is naturally present in fruits and wines. In the present study, the effect of the aroma of EA was evaluated on human breast cancer cell line MDA-MB-231 and normal cell line, Vero. Cell line viability and mechanism of EA cytotoxicity were determined by Trypan blue dye exclusion assay and phase contrast microscopy. It was found that EA at a concentration of 0.026 M was effective in causing considerable cytotoxicity in breast cancer cells (without even coming in contact with the culture medium and cells), while showing no effect on normal cells. Mechanism of action of EA on cancer and Vero cells was investigated by DNA fragmentation and dye binding assays using agarose gel electrophoresis (AGE) and fluorescence microscopy/cytometry, respectively. It was found that EA aroma induced pred...

Frontiers in cellular and infection microbiology, 2016

Staphylococcus aureus (Sau) strains are a main cause of disease, including nosocomial infections ... more Staphylococcus aureus (Sau) strains are a main cause of disease, including nosocomial infections which have been linked to the production of biofilms and the propagation of antibiotic resistance strains such as methicillin-resistant Staphylococcus aureus (MRSA). A previous study found that Streptococcus pneumoniae (Spn) strains kill planktonic cultures of Sau strains. In this work, we have further evaluated in detail the eradication of Sau biofilms and investigated ultrastructural interactions of the biofilmicidal effect. Spn strain D39, which produces the competence stimulating peptide 1 (CSP1), reduced Sau biofilms within 8 h of inoculation, while TIGR4, producing CSP2, eradicated Sau biofilms and planktonic cells within 4 h. Differences were not attributed to pherotypes as other Spn strains producing different pheromones eradicated Sau within 4 h. Experiments using Transwell devices, which physically separated both species growing in the same well, demonstrated that direct contac...

International journal of cardiology, Jan 11, 2016

Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify... more Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers. Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis. No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-...

Nature communications, Aug 25, 2016

Organizers are regions of the embryo that can both induce new fates and impart pattern on other r... more Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development.

Journal of Pharmaceutical Research International

Euphorbia nivulia (EN) one of the members of Euphorbiaceae family, is a medicinal plant of Cholis... more Euphorbia nivulia (EN) one of the members of Euphorbiaceae family, is a medicinal plant of Cholistan Desert (Punjab, Pakistan) that is traditionally used for a number of diseases. The plant is enriched with many phyto-constituents including flavonoids, triterpenes and polyphenols. In present study, crude extract as well as various fractions were assessed for phytochemical analysis, HPLC profiling, radical scavenging property and total phenolic and flavonoid contents. Hydro-alcoholic (70%) crude extract of EN was subjected to fractionation using different solvents including n-hexane, chloroform, butanol and aqueous. After performing the phytochemical screening and HPLC profiling, antioxidant activity was estimated by using DPPH and FRAP assays. Total flavonoid and phenolic contents were also estimated. HPLC analysis confirmed the presence of flavonoids and polyphenols like quercitin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid and ferulic a...

Coronaviruses

Background: The newly emerged delta and omicron variants of severe acute respiratory syndrome cor... more Background: The newly emerged delta and omicron variants of severe acute respiratory syndrome coronavirus (SARS-CoV-2) have affected millions of individuals globally with increased transmissible and infectivity rates. Although, numerous vaccines are available or under clinical trials to combat the SARS-CoV-2 and its variant, still, a therapeutic agent is awaited. Objective: The present work is focused on rigorous screening of chemical constituents of Azadirachta indica (A. indica) against delta and omicron variants of SARS-CoV-2 via inhibition of S-glycoprotein. Methods: Total, 10 compounds of A. indica were subjected to molecular docking and pharmacophore modeling studies against the S-glycoprotein of delta and omicron variants of SARS-CoV-2. Furthermore, homology modeling was performed for omicron S-glycoprotein with the help of SWISS-MODEL and aligned by PyMOL software. Later on, the residues of protein were verified in the allowed region via Ramachandran plot. In addition, our d...

Behavioural Neurology

E-shopping is a rapidly growing phenomenon among different individuals who intend to shop online.... more E-shopping is a rapidly growing phenomenon among different individuals who intend to shop online. However, a trust deficit in the E-shopping environment has always been a critical issue in the brick-and-click mode of shopping, being one of the main reasons for E-cart abandonment in E-commerce. This empirical study is aimed at investigating the perceived effect of website trust on E-shopping intentions and behaviour, drawing upon the theory of planned behaviour (TPB). Data were collected through self-administered questionnaires from working adults who shop for garments online. Structural equation modelling was used to evaluate the model fit and assumptions. Our findings suggest that website trust and E-shopping attitude play substantial roles in building E-shopping intentions and actual behaviours. Both are the significant predictors of the behaviour mediated by E-shopping intentions. However, E-shopping intentions did not mediate between subjective norms and E-shopping behaviour, wh...

Helsingin yliopisto, Mar 5, 2021

This thesis looks into two privacy threats of cellular networks. For their operations, these netw... more This thesis looks into two privacy threats of cellular networks. For their operations, these networks have to deal with unique permanent user identities called International Mobile Subscriber Identity (IMSI). One of the privacy threats is posed by a device called IMSI catcher. An IMSI catcher can exploit various vulnerabilities. Some of these vulnerabilities are easier to exploit than others. This thesis looks into fixing the most easily exploitable vulnerability, which is in the procedure of identifying the subscriber. This vulnerability exists in all generations of cellular networks prior to 5G. The thesis discusses solutions to fix the vulnerability in several different contexts.

Letters in Drug Design & Discovery, 2021

Background: Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic respiratory di... more Background: Coronavirus disease-2019 (COVID-19) has recently emerged as a pandemic respiratory disease with mild to severe pneumonia symptoms. No clinical antiviral agent is available so far. However, several repurposing drugs and vaccines are being given to individuals or in clinical trials against SARS-CoV-2 Objective: The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of SARS-CoV2 encoded proteins via utilizing computational tools. Method: Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic (MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO gap energy and other che...

IOP Conference Series: Materials Science and Engineering, 2020

Electromagnetic forming is a high-velocity forming process in which repulsive forces between cond... more Electromagnetic forming is a high-velocity forming process in which repulsive forces between conducting coil and workpiece are generated by mutual inductance, thus, creating opposite magnetic fields and Lorentz forces on conducting bodies. In such processes, the formability can be enhanced owing to the high-speed deformation of the material. This paper presents a fully-coupled numerical model and experimental study of the deformation behaviour of aluminium alloy (AL3014) using closed die magnetic pulse forming. The current density, magnetic flux density and Lorentz force of 1mm thick sheet were estimated numerically. The effect of deforming sheet on magnetic flux and induction was considered. As a result of which the percentage error in sheet deformation reduced from 10% for the existing uncoupled model to 5% for the fully coupled proposed model.

Journal of Biomolecular Structure and Dynamics, 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coro... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel etiological agent of coronavirus disease 2019 (COVID-19). Nigella sativa, commonly known as black seed or black cumin, has been a historical and traditional plant since thousands of years. Based on their therapeutic efficacy, the chief components of terpenoids and flavonoids were selected from N. sativa seeds and seed oil. This study was designed to check the antiviral efficacy of N. sativa main phytoconstituents against five potential targets of SARS-CoV-2 using in silico structure-based virtual screening approach. Out of twenty five phytocomponents, ten components showed best binding affinity against two viral proteins viz. N-terminal RNA binding domain (NRBD; PDB ID: 6M3M) of nucleocapsid protein and papain-like protease (PL-PRO ; PDB ID: 6W9C) of SARS-CoV-2 using AutoDock 4.2.6, AutoDock Vina and iGEMDOCK. PASS analyses of all ten phytocomponents using Lipinski's Rule of five showed promising results. Further, druglikeness and toxicity assessment using OSIRIS Data Warrior v5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Molecular dynamics simulation study of NRBD of SARS-CoV-2 nucleocapsid protein-alpha-spinasterol complex and PL-PRO-cycloeucalenol complex displayed strong stability at 300 K. Both these complexes exhibited constant root mean square deviation (RMSDs) of protein side chains and Ca atoms throughout the simulation run time. Interestingly, PL-PRO and NRBD are key proteins in viral replication, host cell immune evasion and viral assembly. Thus, NRBD and PL-PRO have the potential to serve as therapeutic targets for N. sativa phytoconstituents in drug discovery process against COVID-19.

Journal of Biomolecular Structure and Dynamics, 2021

There is currently a dearth of specific therapies to treat respiratory infections caused by the t... more There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo. Communicated by Ramaswamy H. Sarma.

Ain Shams Engineering Journal, 2021

Journal of Biomolecular Structure and Dynamics, 2021

A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threate... more A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinski's rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-a and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to proinflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300 K. Both complexes exhibited constant RMSDs of protein side chains and Ca atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further.

Anti-Cancer Agents in Medicinal Chemistry, 2020

Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals ... more Nature is a rich source of natural drug-like compounds with minimal side effects. Phytochemicals better known as “Natural Products” are found abundantly in a number of plants. Since time immemorial, spices have been widely used in Indian cuisine as flavoring and coloring agents. Most of these spices and condiments are derived from various biodiversity hotspots in India (which contribute 75% of global spice production) and form the crux of India’s multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these spices and condiments are known to possess several medicinal properties also. Most of these spices are mentioned in the Ayurveda, the indigenous system of medicine. The antimicrobial, antioxidant, antiproliferative, antihypertensive and antidiabetic properties of several of these natural products are well documented in Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well as anti-inflammatory agents. As...

RNA (New York, N.Y.), Jun 22, 2018

Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their b... more Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their biogenesis and function is still in its infancy. It was recently shown that alternative splicing underlies the formation of circular RNAs (circRNA) arising from the Titin (TTN) gene. Since the main mechanism by which circRNAs are formed is still unclear, we hypothesized that alternative splicing, and in particular exon skipping, is a major driver of circRNA production. We performed RNA sequencing on human and mouse hearts, mapped alternative splicing events and overlaid these with expressed circRNAs at exon-level resolution. In addition, we performed RNA sequencing on hearts of Rbm20 KO mice to address how important Rbm20-mediated alternative splicing is in the production of cardiac circRNAs. In human and mouse hearts, we show that cardiac circRNAs are mostly (~90%) produced from constitutive exons and less (~10%) from alternatively spliced exons. In Rbm20 KO hearts, we identified 38 diff...

Proceedings of the National Academy of Sciences of the United States of America, Jan 19, 2017

Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells... more Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells to form central nervous system (neural plate) or sensory placodes. Grafts of different tissues into the periphery of a chicken embryo elicit different responses: Hensen's node induces a neural plate whereas the head mesoderm induces placodes. How different are these processes? Transcriptome analysis in time course reveals that both processes start by induction of a common set of genes, which later diverge. These genes are remarkably similar to those induced by an extraembryonic tissue, the hypoblast, and are normally expressed in the pregastrulation stage epiblast. Explants of this epiblast grown in the absence of further signals develop as neural plate border derivatives and eventually express lens markers. We designate this state as "preborder"; its transcriptome resembles embryonic stem cells. Finally, using sequential transplantation experiments, we show that the node,...

European Journal of Heart Failure, 2017

AimsPrevious studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for... more AimsPrevious studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF).Methods and resultsRNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)‐1306‐5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time‐points during the study's 1‐year follow‐up. The primary endpoint was the composite of all‐cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR‐1306‐5p...

JACC. Heart failure, Jul 1, 2017

In this study, the authors used biomarker profiles to characterize differences between patients w... more In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. Limited data are available on biomarker profiles in acute HFmrEF. A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with ...

European journal of heart failure, Oct 21, 2017

It is unclear whether distinct pathophysiological processes are present among patients with acute... more It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways. We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal func...

Integrative medicine research, 2017

Aromatherapy is used in clinical settings for patients suffering from several chronic and critica... more Aromatherapy is used in clinical settings for patients suffering from several chronic and critical diseases such as cancer. Ethyl acetate (EA) is a colorless liquid with a characteristic fruity smell and is naturally present in fruits and wines. In the present study, the effect of the aroma of EA was evaluated on human breast cancer cell line MDA-MB-231 and normal cell line, Vero. Cell line viability and mechanism of EA cytotoxicity were determined by Trypan blue dye exclusion assay and phase contrast microscopy. It was found that EA at a concentration of 0.026 M was effective in causing considerable cytotoxicity in breast cancer cells (without even coming in contact with the culture medium and cells), while showing no effect on normal cells. Mechanism of action of EA on cancer and Vero cells was investigated by DNA fragmentation and dye binding assays using agarose gel electrophoresis (AGE) and fluorescence microscopy/cytometry, respectively. It was found that EA aroma induced pred...

Frontiers in cellular and infection microbiology, 2016

Staphylococcus aureus (Sau) strains are a main cause of disease, including nosocomial infections ... more Staphylococcus aureus (Sau) strains are a main cause of disease, including nosocomial infections which have been linked to the production of biofilms and the propagation of antibiotic resistance strains such as methicillin-resistant Staphylococcus aureus (MRSA). A previous study found that Streptococcus pneumoniae (Spn) strains kill planktonic cultures of Sau strains. In this work, we have further evaluated in detail the eradication of Sau biofilms and investigated ultrastructural interactions of the biofilmicidal effect. Spn strain D39, which produces the competence stimulating peptide 1 (CSP1), reduced Sau biofilms within 8 h of inoculation, while TIGR4, producing CSP2, eradicated Sau biofilms and planktonic cells within 4 h. Differences were not attributed to pherotypes as other Spn strains producing different pheromones eradicated Sau within 4 h. Experiments using Transwell devices, which physically separated both species growing in the same well, demonstrated that direct contac...

International journal of cardiology, Jan 11, 2016

Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify... more Circulating microRNAs (miRNAs) emerge as potential heart failure biomarkers. We aimed to identify associations between acute heart failure (AHF)-specific circulating miRNAs and well-known heart failure biomarkers. Associations between 16 biomarkers predictive for 180day mortality and the levels of 12 AHF-specific miRNAs were determined in 100 hospitalized AHF patients, at baseline and 48hours. Patients were divided in 4 pre-defined groups, based on clinical parameters during hospitalization. Correlation analyses between miRNAs and biomarkers were performed and complemented by miRNA target prediction and pathway analysis. No significant correlations were found at hospital admission. However, after 48hours, 7 miRNAs were significantly negatively correlated to biomarkers indicative for a worse clinical outcome in the patient group with the most unfavorable in-hospital course (n=21); miR-16-5p was correlated to C-reactive protein (R=-0.66, p-value=0.0027), miR-106a-5p to creatinine (R=-...

Nature communications, Aug 25, 2016

Organizers are regions of the embryo that can both induce new fates and impart pattern on other r... more Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development.