scholarly journals Plasmodium Falciparum Infection: In Silico Preliminary Studies

Abakós ◽  
2016 ◽  
Vol 5 (1) ◽  
pp. 63
Author(s):  
Andréia Patricia Gomes ◽  
Brenda Silveira Valles Moreira ◽  
Felipe José Dutra Dias ◽  
Victor Hiroshi Bastos Inoue ◽  
Gabriel Vita Silva Franco ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
Ethical Issues ◽  
Plasmodium Knowlesi ◽  
Low Cost ◽  
Plasmodium Malariae ◽  
Infection Process ◽  
Host Cells

<div class="page" title="Page 3"><div class="layoutArea"><div class="column"><p><span>Malaria is an infectious disease of great impact in terms of public health, given the number of people affected and subjected to the risk of illness. Protozoa of the genus Plasmodium cause it and five species can infect humans: </span><em>Plasmodium falciparum</em><span>, </span><em>Plasmodium vivax</em><span>, </span><em>Plasmodium ovale</em><span>, </span><em>Plasmodium malariae </em><span>and </span><em>Plasmodium knowlesi</em><span>; the first is able to produce the most severe cases of the disease. Despite its clinical and epidemiological relevance and investigations in development – targeted at different aspects of the interaction between humans and </span><em>Plasmodium </em><span>protozoa of the genus – there remains many questions about different aspects of the malaria pathophysiology. To study such gaps, interdisciplinary strategies can be pursed, which involve biology, medicine an computer science, as part of the trial </span><span>in silico</span><span>. Such approach provides agility, low cost and does not imply ethical issues that permeate the experiments </span><em>in vitro </em><span>and </span><em>in vivo</em><span>. Based on these considerations, this article presents preliminary results of a computational model of the interaction between </span><em>P. falciparum </em><span>and erythrocytes, implemented in </span><em>AutoSimmune </em><span>system. The results obtained show that the system is able to simulate the host cells infection process by protozoan with similarities with the biological reality. </span></p></div></div></div>

scholarly journals Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Letícia Tiburcio Ferreira ◽  
Juliana Rodrigues ◽  
Gustavo Capatti Cassiano ◽  
Tatyana Almeida Tavella ◽  
Kaira Cristina Peralis Tomaz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Silico ◽  
Antimalarial Activity ◽  
Drug Repositioning ◽  
Dna Gyrase ◽  
Plasmodium Yoelii ◽  
Computer Assisted ◽  
Content Type

ABSTRACT Widespread resistance against antimalarial drugs thwarts current efforts for controlling the disease and urges the discovery of new effective treatments. Drug repositioning is increasingly becoming an attractive strategy since it can reduce costs, risks, and time-to-market. Herein, we have used this strategy to identify novel antimalarial hits. We used a comparative in silico chemogenomics approach to select Plasmodium falciparum and Plasmodium vivax proteins as potential drug targets and analyzed them using a computer-assisted drug repositioning pipeline to identify approved drugs with potential antimalarial activity. Among the seven drugs identified as promising antimalarial candidates, the anthracycline epirubicin was selected for further experimental validation. Epirubicin was shown to be potent in vitro against sensitive and multidrug-resistant P. falciparum strains and P. vivax field isolates in the nanomolar range, as well as being effective against an in vivo murine model of Plasmodium yoelii. Transmission-blocking activity was observed for epirubicin in vitro and in vivo. Finally, using yeast-based haploinsufficiency chemical genomic profiling, we aimed to get insights into the mechanism of action of epirubicin. Beyond the target predicted in silico (a DNA gyrase in the apicoplast), functional assays suggested a GlcNac-1-P-transferase (GPT) enzyme as a potential target. Docking calculations predicted the binding mode of epirubicin with DNA gyrase and GPT proteins. Epirubicin is originally an antitumoral agent and presents associated toxicity. However, its antiplasmodial activity against not only P. falciparum but also P. vivax in different stages of the parasite life cycle supports the use of this drug as a scaffold for hit-to-lead optimization in malaria drug discovery.

Potential Candidates against COVID-19 Targeting RNA-Dependent RNA Polymerase: A Comprehensive Review

2021 ◽  
Vol 22 ◽  
Author(s):  
Neetu Agrawal ◽  
Ahsas Goyal
Keyword(s):  
Rna Polymerase ◽  
In Silico ◽  
Host Cells ◽  
Rna Dependent Rna Polymerase ◽  
In Vivo Experiments ◽  
Contagious Nature ◽  
In Silico Studies ◽  
Viral Enzyme

: Due to the extremely contagious nature of SARS-COV-2, it presents a significant threat to humans worldwide. A plethora of studies are going on all over the world to discover the drug to fight SARS-COV-2. One of the most promising targets is RNA-dependent RNA polymerase (RdRp), responsible for viral RNA replication in host cells. Since RdRp is a viral enzyme with no host cell homologs, it allows the development of selective SARS-COV-2 RdRp inhibitors. A variety of studies used in silico approaches for virtual screening, molecular docking, and repurposing of already existing drugs and phytochemicals against SARS-COV-2 RdRp. This review focuses on collating compounds possessing the potential to inhibit SARS-COV-2 RdRp based on in silico studies to give medicinal chemists food for thought so that the existing drugs can be repurposed for the control and treatment of ongoing COVID-19 pandemic after performing in vitro and in vivo experiments.

scholarly journals In silico prospection of antineoplastic molecules from the Artemisia annua species

2021 ◽  
Vol 7 (19) ◽  
Author(s):  
Isabela Sacienti Lavezo ◽  
Juracy Cirino de Souza Neto ◽  
Túlio Nunes Pinto ◽  
Leonardo Luiz Borges
Keyword(s):  
In Silico ◽  
Artemisia Annua ◽  
Biological Effects ◽  
Low Cost ◽  
Target Prediction ◽  
Molecular Target ◽  
New Drugs ◽  
Antineoplastic Activity

Lung cancer kills the most men and the second that kills the most women (behind only breast cancer). The in silico study makes it possible to search for new drugs at low cost, with a greater possibility of rapid manufacturing and a lower future cost for their manufacture. The objective of this study was to analyze an antineoplastic activity of the compounds of Artemisia annua to obtain an active substance that can reach the molecular target of the cancer cells. Compounds with antineoplastic effects were selected using Scielo, PubMed, and ScienceDirect platforms. Afterward, the first screening of compound compounds was performed with a high ability to predict biological and pharmacological activity through the PASS Prediction, Pubchem, and Swiss ADME platforms. After the current screening, we determined the toxicological and molecular target prediction by the Portox II and Swiss Target Prediction platforms. As a final part, molecular docking and redocking were performed for a compound using the PDB server and the GOLD Suite 5.7.0 program. For another, we completed the pharmacophoric mapping using the Binding DB and PharmaGist database. The compounds scopoletin and caffeic acid were the most promising structures in silico models capable of interacting with EGFR (epidermal growth factor) and MM-9 (metalloproteinase type 9), respectively. The results obtained that these structures are promising to be tested in in vitro and in vivo tests about the antineoplastic activity. In addition, in silico analyses help to understand the biological effects of A. annua extracts regarding antineoplastic evidence.

scholarly journals Identification of Trypanosoma cruzi Growth Inhibitors with Activity In Vivo within a Collection of Licensed Drugs

2021 ◽  
Vol 9 (2) ◽  
pp. 406
Author(s):  
Nieves Martinez-Peinado ◽  
Nuria Cortes-Serra ◽  
Julian Sherman ◽  
Ana Rodriguez ◽  
Juan M. Bustamante ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Specific Activity ◽  
Low Cost ◽  
Chronic Phase ◽  
Vero Cells ◽  
Host Cells ◽  
Vitro Assay ◽  
Specific Selectivity

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects more than six million people worldwide, with its greatest burden in Latin America. Available treatments present frequent toxicity and variable efficacy at the chronic phase of the infection, when the disease is usually diagnosed. Hence, development of new therapeutic strategies is urgent. Repositioning of licensed drugs stands as an attractive fast-track low-cost approach for the identification of safer and more effective chemotherapies. With this purpose we screened 32 licensed drugs for different indications against T. cruzi. We used a primary in vitro assay of Vero cells infection by T. cruzi. Five drugs showed potent activity rates against it (IC50 < 4 µmol L−1), which were also specific (selectivity index >15) with respect to host cells. T. cruzi inhibitory activity of four of them was confirmed by a secondary anti-parasitic assay based on NIH-3T3 cells. Then, we assessed toxicity to human HepG2 cells and anti-amastigote specific activity of those drugs progressed. Ultimately, atovaquone-proguanil, miltefosine, and verapamil were tested in a mouse model of acute T. cruzi infection. Miltefosine performance in vitro and in vivo encourages further investigating its use against T. cruzi.

scholarly journals Potensi Daun Kastuba (Euphorbia Pulcherrima) Sebagai Antimalaria Plasmodium Falciparum

2020 ◽  
Vol 18 (1) ◽  
pp. 1
Author(s):  
ELVINA VERONICA ◽  
NI KADEK SINTA DWI CHRISMAYANTI
Keyword(s):  
Plasmodium Falciparum ◽  
Literature Review ◽  
Combination Therapy ◽  
In Silico ◽  
Artemisinin Combination Therapy ◽  
Ornamental Plants ◽  
Google Scholar ◽  
Euphorbia Pulcherrima

<p><strong>Abstract</strong></p><p><strong>Introduction:</strong> Around 41% of people in the world at risk of malaria due to plasmodium infection. <em>Plasmodium falciparum</em> is the most dangerous malaria infection compared to another plasmodium because it causes 90% of malaria deaths. ACT (Artemisinin Combination Therapy) is the goal standard of malaria medicine, is starting to become resistant, so other alternatives are needed. Poinsettia plants (<em>Euphorbia pulcherrima</em>) are ornamental plants and contain compounds that potential as anti-parasites.</p><p><strong>Objective:</strong> To aims the potential of poinsettia leaves as an antimalarial alternative to <em>Plasmodium falciparum</em> in malaria treatment.</p><p><strong>Methods:</strong> Literature studies using in vivo, in vitro, in silico research articles, and literature reviews from national and international journals accessed from Google Scholar, Elsevier, Science Direct, and Pubmed in the last 10 years using malaria, antioxidants, anti-malaria, <em>Plasmodium falciparum</em>, and <em>Euphorbia pulcherrima</em> as keywords. There were 22 relevant articles used in this literature review.</p><p><strong>Results:</strong> Antioxidants in poinsettia leaves inhibited plasmodium growth by inhibit nutrient transport at new permeation pathways and prevent hemozoin ban. Terpenoids in poinsettia inhibit schizont and trophozoite in an earlier asexual phase of <em>Plasmodium falciparum</em> by inhibiting isoprenoid biosynthesis.</p><p><strong>Conclusion:</strong> Poinsettia (<em>Euphorbia pulcherrima</em>) has the potency to be an antimalarial alternative against <em>Plasmodium falciparum</em>. Need further research about the dosage and side effects of the usage.</p><p><strong>Key words:</strong> Malaria, antioxidants, anti-malaria, <em>Plasmodium falciparum</em>, <em>Euphorbia pulcherrima</em></p><p><strong>Abstrak</strong></p><p><strong>Pendahuluan:</strong> Sebesar 41% penduduk di dunia berisiko terkena malaria akibat infeksi plasmodium. Infeksi malaria akibat <em>Plasmodium falciparum</em> merupakan infeksi paling berbahaya dibandingkan plasmodium lainnya karena menyebabkan 90% kematian malaria. obat malaria ACT (<em>Artemisinin Combination Therapy</em>) yang merupakan pengobatan goal standar obat malaria kini mulai resistensi sehingga diperlukan alternatif lainnya. Tanaman kastuba (<em>Euphorbia pulcherrima</em>) merupakan tanaman hias dan memiliki kandungan senyawa antioksidan yang berpotensi sebagai anti parasit.</p><p><strong>Tujuan</strong>: mengetahui potensi daun kastuba sebagai alternatif antimalarial <em>Plasmodium falciparum</em> dalam pengobatan malaria.</p><p>Metode: Studi literatur menggunakan artikel penelitian in vivo, in vitro, in silico, dan artikel tinjauan pustaka dari jurnal nasional dan internasional yang diakses dari Google Scholar, Elsevier, Science Direct, dan Pubmed 10 tahun terakhir menggunakan kata kunci malaria, antioksidan, anti-malaria, <em>Plasmodium falciparum</em>, <em>Euphorbia pulcherrima</em>. Digunakan 22 artikel yang relevan dalam <em>literature review</em> ini.</p><p><strong>Hasil:</strong> Antioksidan tanaman kastuba menghambat perkembangan plasmodium dengan menghambat transport nutrisi jalur permeasi baru dan mencegah pembentukan hemozoin. Terpenoid dalam tanaman kastuba menghambat pembentukan skizon dan tropozoit fase aseksual <em>Plasmodium falciparum</em> dengan menghambat biosintesis isoprenoid.</p><p><strong>Kesimpulan:</strong> Tanaman kastuba (<em>Euphorbia pulcherrima</em>) berpotensi sebagai alternatif antimalarial terhadap <em>Plasmodium falciparum</em>. Perlu penelitian lebih lanjut terutama dalam dosis dan efek samping penggunaannya.</p><p><strong>Kata kunci</strong>: Malaria, antioksidan,<em> anti-malaria, Plasmodium falciparum, Euphorbia pulcherrima </em></p>

scholarly journals Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9

2016 ◽  
Vol 60 (5) ◽  
pp. 2696-2708 ◽  
Author(s):  
Suvadip Mallick ◽  
Aritri Dutta ◽  
Ankur Chaudhuri ◽  
Debasri Mukherjee ◽  
Somaditya Dey ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
In Silico ◽  
Antileishmanial Activity ◽  
Host Cells ◽  
Cell Mediated Immunity ◽  
Interleukin 17 ◽  
Content Type ◽  
Tlr9 Agonist

ABSTRACTIn our previous report, we showed that astrakurkurone, a triterpene isolated from the Indian mushroomAstraeus hygrometricus(Pers.) Morgan, induced reactive oxygen species, leading to apoptosis inLeishmania donovanipromastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 μg/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activityin vitroandin vivo. Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied byin vitroassay in the presence of a TLR9 agonist and antagonist and byin silicomodeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression ofL. donovani-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified byin silicoevidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burdenin vivoby inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearancein vitroandin vivo.

scholarly journals In Vitro and In Vivo Characterization of a Bordetella bronchiseptica Mutant Strain with a Deep Rough Lipopolysaccharide Structure

2002 ◽  
Vol 70 (4) ◽  
pp. 1791-1798 ◽  
Author(s):  
Federico Sisti ◽  
Julieta Fernández ◽  
María Eugenia Rodríguez ◽  
Antonio Lagares ◽  
Nicole Guiso ◽  
...  
Keyword(s):  
Parental Strain ◽  
Infection Process ◽  
Bordetella Bronchiseptica ◽  
Host Cells ◽  
Virulence Determinants ◽  
Chronic Infections ◽  
In Vivo Experiments ◽  
Dominant Phenotype

ABSTRACT Bordetella bronchiseptica is closely related to Bordetella pertussis, which produces respiratory disease primarily in mammals other than humans. However, its importance as a human pathogen is being increasingly recognized. Although a large amount of research on Bordetella has been generated regarding protein virulence factors, the participation of the surface lipopolysaccharide (LPS) during B. bronchiseptica infection is less understood. To get a better insight into this matter, we constructed and characterized the behavior of an LPS mutant with the deepest possible rough phenotype. We generated the defective mutant B. bronchiseptica LP39 on the waaC gene, which codes for a heptosyl transferase involved in the biosynthesis of the core region of the LPS molecule. Although in B. bronchiseptica LP39 the production of the principal virulence determinants adenylate cyclase-hemolysin, filamentous hemagglutinin, and pertactin persisted, the quantity of the two latter factors was diminished, with the levels of pertactin being the most greatly affected. Furthermore, the LPS of B. bronchiseptica LP39 did not react with sera obtained from mice that had been infected with the parental strain, indicating that this defective LPS is immunologically different from the wild-type LPS. In vivo experiments demonstrated that the ability to colonize the respiratory tract is reduced in the mutant, being effectively cleared from lungs within 5 days, whereas the parental strain survived at least for 30 days. In vitro experiments have demonstrated that, although B. bronchiseptica LP39 was impaired for adhesion to human epithelial cells, it is still able to survive within the host cells as efficiently as the parental strain. These results seem to indicate that the deep rough form of B. bronchiseptica LPS cannot represent a dominant phenotype at the first stage of colonization. Since isolates with deep rough LPS phenotype have already been obtained from human B. bronchiseptica chronic infections, the possibility that this phenotype arises as a consequence of selection pressure within the host at a late stage of the infection process is discussed.

scholarly journals Antimalarial Activity of Curcuma Caesia Against 3D7 and K1 Strains of Plasmodium Falciparum

2020 ◽  
Author(s):  
Monika Chaturvedi ◽  
Reena Rani ◽  
Dushyant Sharma ◽  
Jaya Parkash Yadav
Keyword(s):  
Plasmodium Falciparum ◽  
Ethyl Acetate ◽  
In Silico ◽  
Antimalarial Activity ◽  
Antimalarial Drugs ◽  
Mechanism Study ◽  
Effective Development ◽  
Ethyl Acetate Extracts

Abstract Background: Malaria is a severe and sometimes mortal tropical disease that spreads through parasites. The purpose of the study was to evaluate in vitro and in-silicoantiplasmodial potential of Curcuma caesia extracts against Plasmodium falciparum.Methods: Lack of a vaccine and the widespread resistance to antimalarial drugs have resulted in emphasis on novel antimalarial drugs development. Ethyl acetate and methanol extracts of Curcuma caesia were prepared and analysed for their antiplasmodial activity against Chloroquine sensitive (3D7) and resistant (K1) strains of P. falciparumusingfluorescence-based SYBR Green assay. The cytotoxicity tests were carried out using the verocell lines by MTT assay.The phosphoethanolamine methyltransferase enzyme ((PfPMT) essential for growth of Plasmodium falciparum was used as protein target for in-silicostudy.Result: Curcuma caesia ethyl acetate extracts showedpotentantiplasmodial activitywith IC50 values of 3.37 µg/ml and 1.53 µg/ml against 3D7 and K1 strain respectively.Docking results show that β-selinenol an oxygenized sesquiterpene had the free binding energy of -6.76 Kcal/mol.Conclusion: Sesquiterpene present in the Curcuma caesia extract was responsible for antimalarial potential analyzed by molecular modeling. The present findings, however preliminary in nature. Further studies are required to proven the antimalarial efficacy C. caesia by isolating the active compounds and in vivo mechanism study that may contribute to more effective development of antimalarial drugs in the future.

Antigens ofAspergillus fumigatusexpressed during infection

1995 ◽  
Vol 73 (S1) ◽  
pp. 1087-1091 ◽  
Author(s):  
Jean-Paul Debeaupuis ◽  
Jacqueline Sarfati ◽  
Hidemitsu Kobayashi ◽  
Drion G. Boucias ◽  
Anne Beauvais ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Virulence Gene ◽  
Culture Conditions ◽  
Infection Process ◽  
Host Cells ◽  
Virulence Determinants

Aspergillus fumigatus secretes an array of antigenic molecules in vitro and in vivo. Recent progresses have been made in the characterization and standardization of A. fumigatus antigens useful for the serodiagnosis of aspergillosis. The chymotrypsin antigen has been purified and can be utilized for the diagnosis of aspergillosis occurring in patients with an immunocompetent B cell population. In the case of immunosuppressed patients suffering from invasive aspergillosis, new methods have been developed to detect the galactofuran containing antigen in the serum. The chemical configuration of this molecule is now known. In contrast to their potential in diagnosis, very little progress has been made on the study of the biochemical and pathoimmunological role of these antigens during the infection process. Two reasons can be advanced for this lack of understanding of the virulence determinants. First of all, antigens studied have been produced in vitro in a dextrose rich medium where pH reaches a value below 5 at maximal growth. These culture conditions are very different from the nutritional environment of the lung, which is a protein-based medium with a slightly basic pH. Antigens expressed under these nutritional conditions are very different from the ones detected in vitro. Second, A. fumigatus is an opportunistic fungus which is characterized by a multifactorial virulence. Gene disruption strategy is not adequate to discriminate the role of a factor in the virulence of the fungus. In contrast, as shown by the studies on two toxins of A. fumigatus, a direct effect of an antigen can be seen directly when several fungal molecules are tested in conjunction on host cells. Key words: Aspergillus fumigatus, antigen, invasive aspergillosis, galactomannan, protease.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

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