Search results for: Viral
#33073716 2020/10/19 To Up
A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets.Despite the continued global spread of the current COVID-19 pandemic, the nonavailability of a vaccine or targeted drug against this disease is still prevailing. The most established mechanism of viral entry into the body is considered to be via angiotensin-converting enzyme 2 (ACE2) acting as a receptor for viral spike protein thereby facilitating its entry in the cell. However, ACE2 is also involved in providing the protection from severe pathological changes. This article provides a computational and bioinformatics-based analysis of ACE2 with an objective of providing further insight into the earnest efforts to determine its true position in COVID-19 pathology. The results of this study show that ACE2 has strikingly low expression in healthy human lung tissue and was absent from the list of differentially expressed genes. However, when transcription factors were analyzed, we found a significant upregulation of FOS and downregulation of FOXO4 and FOXP2. Moreover, the miRNA prediction analysis revealed that miR-1246, whose upregulation has been experimentally established to be a cause of acute respiratory distress syndrome (ARDS), was found to be targeting the coding DNA sequence (CDS) of ACE2. This study presents a wide range of potentially important transcription factors as well as miRNA targets associated with ACE2 which can be potentially used for drug designing amid this challenging pandemic situation. Communicated by Ramaswamy H. Sarma.
Abeedha Tu-Allah Khan, Zumama Khalid, Hafsa Zahid, Muhammad Abrar Yousaf, Abdul Rauf Shakoori
2405 related Products with: A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets.100 mg0.1ml (1mg/ml)1000 25 MG
#33073705 2020/10/19 To Up
Designed thiazolidines: an arsenal for the inhibition of nsP3 of CHIKV using molecular docking and MD simulations.Chikungunya virus (CHIKV) belongs to the alpha virus and it's infection in humans causes fever, known as chikungunya fever (CHIKF). It is a sudden onset of fever and may affect humans badly. The mode of transmission to human occurs due to the biting of the mosquitoes. Till date, thousands of humans are affected from this virus throughout the world. As on date, no promising medicine or vaccine is available in the market to cure from this viral infection. Therefore, there is a need of promising candidate against the nsp3 of CHIKV. In the present work, a library of the compounds are designed based on the product obtained in a multi-component reaction. Then, the designed compounds are filtered based on binding energy against the nsp3 of CHIKV obtained using molecular docking. Further, to understand the interaction of nsp3 of CHIKV and screened compound, CMPD474, the molecular dynamics MD) simulations at different temperatures, that is, 300, 325, 350, 375, and 400 K is performed. The binding or the formation of the complex is studied through different trajectories obtained from MD simulations. The accurate information for the binding energy is determined by performing MM-GBSA calculations and the best inhibition was observed at 300 K as the change in free energy for the formation of the complex is -7.0523 kcal/mol. Communicated by Ramaswamy H. Sarma.
Mahendra Kumar Meena, Durgesh Kumar, Abhilash Jayaraj, Ajay Kumar, Kamlesh Kumari, L M Katata-Seru, Indra Bahadur, Vinod Kumar, Anjali Sherawat, Prashant Singh
1848 related Products with: Designed thiazolidines: an arsenal for the inhibition of nsP3 of CHIKV using molecular docking and MD simulations.100 μg500 0.1 ml100 mg100ug1 ml10 mg100ul100ug100 μg10 mg100 μg
#33073694 2020/10/17 To Up
Comparison of Transgenic and Adenovirus hACE2 Mouse Models for SARS-CoV-2 Infection.Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide pandemic with high morbidity and mortality. Development of animal models that recapitulate important aspects of coronavirus disease 2019 (COVID-19) is critical for the evaluation of vaccines and antivirals, and understanding disease pathogenesis. SARS-CoV-2 has been shown to use the same entry receptor as SARS-CoV-1, human angiotensin-converting enzyme 2 (hACE2)(1-3). Due to amino acid differences between murine and hACE2, inbred mouse strains fail to support high titer viral replication of SARS-CoV-2 virus. Therefore, a number of transgenic and knock-in mouse models, as well as viral vector-mediated hACE2 delivery systems have been developed. Here we compared the K18-hACE2 transgenic model to adenovirus-mediated delivery of hACE2 to the mouse lung. We show that K18-hACE2 mice replicate virus to high titers in the nasal turbinates, lung and brain, with high lethality, and cytokine/chemokine production. In contrast, adenovirus-mediated delivery results in viral replication to lower titers limited to the nasal turbinates and lung, and no clinical signs of infection with a challenge dose of 10 plaque forming units. The K18-hACE2 model provides a stringent model for testing the ability of vaccines and antivirals to protect against disease, whereas the adenovirus delivery system has the flexibility to be used across multiple genetic backgrounds and modified mouse strains.
Raveen Rathnasinghe, Shirin Strohmeier, Fatima Amanat, Virginia L Gillespie, Florian Krammer, Adolfo García-Sastre, Lynda Coughlan, Michael Schotsaert, Melissa Uccellini
1392 related Products with: Comparison of Transgenic and Adenovirus hACE2 Mouse Models for SARS-CoV-2 Infection.200ug1 mg200ug100ug50 ug Product tipe: Antib100ug Lyophilized0.2 mg25ml 2x5L200ug100 ul
#33073687 // To Up
Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid.Entry of circovirus into the host cell nucleus is essential for viral replication during the early stage of infection. However, the mechanisms by which nucleolar shuttle proteins are used during viral replication is still not well understood. Here, we report a previously unidentified nucleolar localization signal in circovirus capsid protein (Cap), and that circovirus hijacks the nucleolar phosphoprotein nucleophosmin-1 (NPM1) to facilitate its replication. Colocalization analysis showed that NPM1 translocates from the nucleolus to the nucleoplasm and cytoplasm during viral infection. Coimmunoprecipitation and glutathione -transferase pull-down assays showed that Cap interacts directly with NPM1. Binding domain mapping showed that the arginine-rich N-terminal motif MTYPYHPSHLG of Cap, and residue serine-48 of the N-terminal oligomerization domain of NPM1, are essential for the interaction. Virus rescue experiments showed that all arginine to alanine substitution in the N-terminal arginine-rich motif of Cap resulted in diminished viral replication. Knockdown of and substitution of serine-48 in NPM1 to glutamic acid also decreased viral replication. In addition, binding assays showed that the arginine-rich motif of Cap is a nucleolar localization signal. Taken together, our findings demonstrate that circovirus protein Cap is a nucleolus-located, and regulates viral replication by directly binding to NPM1.
Jianwei Zhou, Yadong Dai, Cui Lin, Ying Zhang, Zixuan Feng, Weiren Dong, Yulan Jin, Yan Yan, Jiyong Zhou, Jinyan Gu
1155 related Products with: Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid.100 ul0.1 mg 100ul0.25 mg0.1 mg 100ul100 ul0.2 mg100ug Lyophilized100ug Lyophilized20 μg100ug Lyophilized
#33073673 2020/10/19 To Up
HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4 T cell death.The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4 T lymphocyte cell death. The viral envelope glycoproteins (Env), expressed at the surface of infected cells, play a key role in this process. Env triggers macroautophagy/autophagy, a process necessary for subsequent apoptosis, and the production of reactive oxygen species (ROS) in bystander CD4 T cells. Here, we demonstrate that Env-induced oxidative stress is responsible for their death by apoptosis. Moreover, we report that peroxisomes, organelles involved in the control of oxidative stress, are targeted by Env-mediated autophagy. Indeed, we observe a selective autophagy-dependent decrease in the expression of peroxisomal proteins, CAT and PEX14, upon Env exposure; the downregulation of either BECN1 or SQSTM1/p62 restores their expression levels. Fluorescence studies allowed us to conclude that Env-mediated autophagy degrades these entire organelles and specifically the mature ones. Together, our results on Env-induced pexophagy provide new clues on HIV-1-induced immunodeficiency. Ab: antibodies; AF: auranofin; AP: anti-proteases; ART: antiretroviral therapy; BafA: bafilomycin A; BECN1: beclin 1; CAT: catalase; CD4: CD4 molecule; CXCR4: C-X-C motif chemokine receptor 4; DHR123: dihydrorhodamine 123; Env: HIV-1 envelope glycoproteins; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFP-SKL: GFP-serine-lysine-leucine; HEK: human embryonic kidney; HIV-1: type 1 human immunodeficiency virus; HTRF: homogeneous time resolved fluorescence; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NAC: N-acetyl-cysteine; PARP: poly(ADP-ribose) polymerase; PEX: peroxin; ROS: reactive oxygen species; siRNA: small interfering ribonucleic acid; SQSTM1/p62: sequestosome 1.
Coralie F Daussy, Mathilde Galais, Baptiste Pradel, Véronique Robert-Hebmann, Sophie Sagnier, Sophie Pattingre, Martine Biard-Piechaczyk, Lucile Espert
2748 related Products with: HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4 T cell death.100ug Lyophilized100ug/vial 100ul100ug Lyophilized100ug/vial1000 tests25 mg100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized100ug Lyophilized
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#33073571 2020/10/18 To Up
Gold/Silver Hybrid Nanoparticles with Enduring Inhibition of Coronavirus Multiplication through Multisite Mechanisms.As a large enveloped RNA virus, coronavirus is of considerable medical and veterinary significance, and anticoronavirus treatment is challenging due to its biodiversity and rapid variability. In this study, [email protected] nanorods ([email protected]) were successfully synthesized by coating AuNRs with silver and were shown for the first time to have activity against the replication of porcine epidemic diarrhea virus (PEDV). Viral titer analysis demonstrated that [email protected] could inhibit PEDV infection by 4 orders of magnitude at 12 h post-infection, which was verified by viral protein expression analysis. The potential mechanism of action showed that [email protected] could inhibit the entry of PEDV and decrease the mitochondrial membrane potential and caspase-3 activity. Additionally, we demonstrated that a large amount of virus proliferation can cause the generation of reactive oxygen species in cells, and the released Ag and exposed AuNRs by [email protected] after the stimulation of reactive oxygen species has superior antiviral activity to ensure long-term inhibition of the PEDV replication cycle. The integrated results support that [email protected] can serve as a potential therapeutic strategy to prevent the replication of coronavirus.
Ting Du, Jinyu Zhang, Chunqiao Li, Tao Song, Ping Li, Jifeng Liu, Xinjun Du, Shuo Wang
1468 related Products with: Gold/Silver Hybrid Nanoparticles with Enduring Inhibition of Coronavirus Multiplication through Multisite Mechanisms.96 reactions100ug100ug Lyophilized100ug Lyophilized5mg100ug100ug Lyophilized100ug Lyophilized5mg100ug100ug Lyophilized
#33073569 2020/10/19 To Up
Serinol-Based Benzoic Acid Esters as New Scaffolds for the Development of Adenovirus Infection Inhibitors: Design, Synthesis, and Biological Evaluation.Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. In this context, there is an urgent need to develop effective anti-HAdV drugs with suitable therapeutic indexes. In this work, we identified new serinol-derived benzoic acid esters as novel scaffolds for the inhibition of HAdV infections. A set of 38 compounds were designed and synthesized, and their antiviral activity and cytotoxicity were evaluated. Four compounds (, , , and ) inhibited HAdV infection at low micromolar concentrations (2.82-5.35 μM). Their half maximal inhibitory concentration (IC) values were lower compared to that of cidofovir, the current drug of choice. All compounds significantly reduced the HAdV DNA replication process, while they did not block any step of the viral entry. Our results showed that compounds , , and seem to be targeting the expression of the E1A early gene. Moreover, all four derivatives demonstrated a significant inhibition of human cytomegalovirus (HCMV) DNA replication. This new scaffold may represent a potential tool useful for the development of effective anti-HAdV drugs.
Sarah Mazzotta, Judith Berastegui-Cabrera, Gabriele Carullo, Margarita Vega-Holm, Marta Carretero-Ledesma, Lara Mendolia, Francesca Aiello, Fernando Iglesias-Guerra, Jerónimo Pachón, José Manuel Vega-Pérez, Javier Sánchez-Céspedes
1049 related Products with: Serinol-Based Benzoic Acid Esters as New Scaffolds for the Development of Adenovirus Infection Inhibitors: Design, Synthesis, and Biological Evaluation.100100 μl 25 G100 assays100tests 1 G100ug Lyophilized 100 G500 mg100
#33073557 2020/10/19 To Up
Biobanking for COVID-19 research.Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick as possible to allow for implementation of science-based preventive, diagnostic, prognostic and therapeutic strategies.
Patrizia Rovere-Querini, Cristina Tresoldi, Caterina Conte, Annalisa Ruggeri, Silvia Ghezzi, Rebecca De Lorenzo, Luigi Di Filippo, Nicola Farina, Giuseppe A Ramirez, Marco Ripa, Nicasio Mancini, Elisa Cantarelli, Laura Galli, Andrea Poli, Francesco De Cobelli, Chiara Bonini, Angelo A Manfredi, Stefano Franchini, Marzia Spessot, Michele Carlucci, Lorenzo Dagna, Paolo Scarpellini, Alberto Ambrosio, Davide Di Napoli, Emanuele Bosi, Moreno Tresoldi, Adriano Lazzarin, Giovanni Landoni, Gianvito Martino, Alberto Zangrillo, Guido Poli, Antonella Castagna, Elisa Vicenzi, Massimo Clementi, Fabio Ciceri, 1 G100μg1 mg 25 G250 mg1 mg0.1ml (1mg/ml)2x96100ug 25 G25 g
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#33073555 2020/10/19 To Up
SARS-CoV-2-related lung pathology: macroscopic and histologic features and their clinical implications.The ongoing global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been posing challenges to proper patients' management. Lungs are the first, and often the most affected organ by SARS-CoV-2; viral infection involves and damages both epithelial and vascular compartments, sometimes leading to severe and even fatal acute respiratory distress syndrome. Histopathological findings, mainly from postmortem examination of COVID-19 deceased patients, have been increasingly published in the last few months, helping to elucidate the sequence of events resulting in organ injury, and the complex multifactorial pathogenesis of this novel disease. A multidisciplinary approach to autopsy, including light microscopy examination along with the detection of viral proteins and/or RNA in tissue samples through ancillary techniques, provided crucial information on the mechanisms underlying the often-heterogeneous clinical picture of COVID-19.
Francesca Sanguedolce, Magda Zanelli, Stefano Ascani, Maurizio Zizzo, Simona Tortorella, Alessandra Soriano, Alberto Cavazza, Francesco Sollitto, Domenico Loizzi
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