Creative Biostructure’s Post

Epitranscriptomic m5C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection Science Advances https://lnkd.in/gp5DuF48

New preprint from the lab, plus loads of fabulous collaborators, describing how most poxviruses, including avipoxviruses, antagonise DNA-PK to block cGAS/STING-dependent interferon production during infection. These viruses disrupt the interaction between DNA-PK and DNA thereby inhibiting sesnsing of viral DNA. This immune evasion mechanism is conserved across a broader range of species than other poxvirus antagonists, which may reflect the difficulty in evolving escape mechanisms that interfere with a protein that is essential for maintenance of genomic stability. This could also be relevant to the severity of mpox, as the milder clade II virus has lost one of the genes that inhibits DNA-PK. The clade Ib virus has kept this gene and will therefore be able to block host immune responses more effectively. https://lnkd.in/ei-WeMZr

Influenza viruses are major human pathogens which cause annual epidemics (type A, B and C viruses) and have zoonotic and pandemic potential (type A viruses). The viral RNA dependent RNA polymerase (FluPol) is a key determinant of viral host-range and pathogenicity, and a prime target for antiviral drugs. It is a ~260 kDa heterotrimer composed of the subunits PB1 (polymerase basic protein 1), PB2 (polymerase basic protein 2) and PA (polymerase acidic protein). In viral particles each of the eight negative-sense RNA genomic segments (vRNAs) is associated with one copy of the viral polymerase and encapsidated with multiple copies of the nucleoprotein (NP) to form viral ribonucleoproteins (vRNPs). Upon viral infection, incoming vRNPs are imported into the nucleus in which FluPol performs transcription and replication of the viral genome through distinct primed and unprimed mechanisms. FluPol associates dynamically with many cellular proteins, among which the interaction with the host RNAP II transcription machinery. The FluPol CTD-binding interface is essential not only for transcription but also for replication of the viral genome. Here you can see a cryoEM structure of the Influenza A/H7N9 polymerase symmetric dimer bound to a promoter sequence (PDB code: 8POH) Rendering by Francisco J. Enguita (@paco.enguita) made with #proteinimager https://lnkd.in/dfqh2nv2 #molecularart #influenza #polymerase #dimer #promoter #cryoem

📃Scientific paper: Sialic acids and viruses Abstract: Let us study viruses and the role of sialic acids in their first step of reproduction, the attachment to cells. We begin our study with the help of the "Earth's virology course", created by Vincent Racaniello, with David Tuller and Gertrud U. Rey. The first virus that we will study is that of influenza A. Actually, "Earth's virology course" is a proper starting point for learning the mechanisms the virus uses to attach and enter the host cells. In the case of the influenza virus, its spike protein is used to attach the virion to sialic acid receptors of the host cells. Then we will consider coronaviruses, with the help of literature about the role of sialic acids in their attachment by means of spike proteins. In fact, there are seven human coronavirus, and they use sialic acid or angiotensin-converting enzyme 2 (ACE2) or other receptors or a combination of them. We can find in literature that Sars-Cov-2 virus can use sialic acid too for the attachment to cells, but its main target is considered the ACE2 receptor.;See please the new version. I have revised the discussion about hemmaglutinin esterase in coronaviruses. I have also added figures and references. --- The study in 10.1021/acscentsci.0c00855 used a glyco-nanoparticle platform, discovering that N-acetyl neuraminic acid has affinity toward the SARS-COV-2 spike glycoprotein, that is a glycan-binding function. However, a recent study, 10.1016/j.scib.2021.01.010, which has investigated the binding of the s... Continued on ES/IODE ➡️ https://etcse.fr/W3q ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

https://lnkd.in/gaX7bWa5 Happy to publish the article titled "Non-Nucleoside Lycorine-Based Analogs as Potential DENV/ZIKV NS5 Dual Inhibitors" discusses the use of lycorine analogs to target the NS5 RNA-dependent RNA polymerase of dengue and Zika viruses. Through virtual screening, molecular dynamics, and ADMET analysis, the study identified 12 promising lycorine analogs, which showed superior binding affinities compared to ribavirin. These analogs, especially those with distinct enantiomers, present promising avenues for antiviral development against both viruses. Great work with Luke Achenie in Virginia Tech, Paola Andrea Caicedo Burbano in ICESI, Andrés Felipe Vásquez Jiménez, Maria Francisca Villegas-Torres, Yasser Hayek Orduz, Adrian_Camilo Rodríguez_Ararat, Felipe Sierra Hurtado

"Many studies have shown that macrophages can internalize viruses and degrade them in lysosomes for clearance in vivo. Inspired by these natural behaviors and using SARS-CoV-2 as a testbed, researchers harvest lysosomes from activated macrophages and anchor the protein-receptor ACE2 as bait, thus constructing a lysosomal “TRAP” (lysoTRAP) that selectively captures, internalizes, and eventually degrades SARS-CoV-2. Through experiments with cells, female mice, female hamsters, and human lung organoids, we demonstrate that lysoTRAP effectively clears SARS-CoV-2." https://lnkd.in/eXybvhWX #lysosomes #virus clearance

Influenza viruses are major human pathogens which cause annual epidemics (type A, B and C viruses) and have zoonotic and pandemic potential (type A viruses). The viral RNA dependent RNA polymerase (FluPol) is a key determinant of viral host-range and pathogenicity, and a prime target for antiviral drugs. It is a ~260 kDa heterotrimer composed of the subunits PB1 (polymerase basic protein 1), PB2 (polymerase basic protein 2) and PA (polymerase acidic protein). In viral particles each of the eight negative-sense RNA genomic segments (vRNAs) is associated with one copy of the viral polymerase and encapsidated with multiple copies of the nucleoprotein (NP) to form viral ribonucleoproteins (vRNPs). Upon viral infection, incoming vRNPs are imported into the nucleus in which FluPol performs transcription and replication of the viral genome through distinct primed and unprimed mechanisms. FluPol associates dynamically with many cellular proteins, among which the interaction with the host RNAP II transcription machinery. The FluPol CTD-binding interface is essential not only for transcription but also for replication of the viral genome. Here you can see a cryoEM structure of the Influenza A/H7N9 polymerase symmetric dimer bound to a promoter sequence (PDB code: 8POH) Rendering by Francisco J. Enguita (@paco.enguita) made with #proteinimager https://lnkd.in/dpsZPtFd #molecularart #influenza #polymerase #dimer #promoter #cryoem

Virology Lectures 2024 #15: Mechanisms of Pathogenesis 🦠 The development of disease in a host, viral pathogenesis, is the outcome of both viral reproduction and the immune response. In this lecture we discuss how to measure viral virulence, and how to identify viral and host genes that regulate it. Specific mechanisms by which CD8 T cells, CD4 T cells and antibodies cause immunopathology, and how virus infections lead to immunosuppression are discussed. 📺 https://bit.ly/3TzC33c

🦠SARS-CoV-2 protein detectable in COVID-19 patients up to 14 months after illness🧬 By Caitlyn Stulpin Fact checked by Carol L. DiBerardino, MLA, ELS Key takeaways: Of plasma samples taken after COVID-19 infection, 7.5% to 12.6% contained detectable viral antigens. Researchers also found evidence of SARS-CoV-2 spike RNA in patients’ guts up to 2 years after infection. “SARS-CoV-2 #antigens persist in patients with #COVID-19 for months to years after infection.” Researchers, “found evidence of double-stranded #RNA, which should be present only if the #virus is undergoing active #replication, according to Peluso. He said this suggests that the genetic material “may not just be inert and may actually reflect an #active reservoir of #SARS-CoV-2.”

Delighted to share our new review paper titled "Viral deubiquitinating proteases and the promising strategies of their inhibition", published last week in Virus Research as part of the Nidoviruses special issue! In this review, we discuss the viral proteases with deubiquitinating activity known to date, their importance in viral replication and innate immune evasion, as well as ways in which we might inhibit such proteases to fight these viruses. Thanks to the co-authors for their contribution!