• Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. (medscape.com)
  • Corticosteroids have no impact on cold symptoms and may actually increase viral replication. (medscape.com)
  • It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. (wikipedia.org)
  • Several drugs are either on the market or in various stages of research target NS5B as a means to prevent further viral RNA replication and thus treat or cure HCV. (wikipedia.org)
  • HIV-1 replication in macrophages and microglia involves intracellular assembly and budding into modified subsets of multivesicular bodies (MVBs), which support both viral persistence and spread. (nature.com)
  • Recently, amyloid precursor protein (APP) was identified as an inhibitor of HIV-1 replication in macrophages and microglia via an unknown mechanism. (nature.com)
  • Processing of C99, entry of Gag into MVBs and release of infectious virus could be suppressed by expressing ubiquitination-defective C99 or by γ-secretase inhibitor treatment, suggesting that APP's amyloidogenic pathway functions to sense and suppress HIV-1 replication in macrophages and microglia. (nature.com)
  • We here report on a comparative study of the antipoliovirus activity of a selection of molecules that have previously been reported to be inhibitors of picornavirus replication and discuss their potential use, alone or in combination, for the treatment or prophylaxis of poliovirus infection. (cdc.gov)
  • A substantial number of small molecule compounds have been reported as potent inhibitors of the replication of picornaviruses in vitro ( 8 ). (cdc.gov)
  • Endonuclease inhibitors interfere with viral RNA transcription and block virus replication in both influenza A and B viruses. (cdc.gov)
  • Here, we describe a mechanism to inhibit the replication of the oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV), by targeting the ATP-dependent formation of viral ribonucleoprotein particles (vRNPs). (nature.com)
  • We demonstrate that small-molecule inhibitors which selectively inhibit the ATPase activity of the cellular human transcription/export complex (hTREX) protein UAP56 result in effective inhibition of vRNP formation, viral lytic replication and infectious virion production. (nature.com)
  • Background: Glucoregulatory protein 94 (Grp94) is necessary for the post-viral life cycle and plays a quality control role in viral proteins, but the role of Grp94 in regulating viral replication in host cells is not well known. (eurekaselect.com)
  • Therefore, finding a compound that can regulate Grp94 will help us to study the mechanism of viral replication. (eurekaselect.com)
  • We suppose that HCP1 may inhibit viral replication. (eurekaselect.com)
  • Objective: This study aimed to investigate the effect of HCP1 on the replication ability of Senecavirus A (SVA), so as to provide a target and a leading compound for revealing the pathogenic mechanism of the virus and developing antiviral drugs. (eurekaselect.com)
  • In addition, SVA infection can lead to an increased level of autophagy, and HCP1 can inhibit host cell autophagy caused by SVA infection, thereby inhibiting viral replication and infection. (eurekaselect.com)
  • Conclusion: These findings reveal that Grp94 is a key factor in controlling SVA replication, and its inhibitor HCP1 suppresses SVA replication by inhibiting the increase of Grp94 protein level and autophagy induced by SVA. (eurekaselect.com)
  • Role of RNA structures present at the 3′UTR of dengue virus on translation, RNA synthesis, and viral replication. (microbiologyresearch.org)
  • Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. (microbiologyresearch.org)
  • Hepatitis B and hepatitis C virus replication upregulates serine protease inhibitor Kazal, resulting in cellular resistance to serine protease-dependent apoptosis. (nih.gov)
  • Our recent studies have suggested that replication of either of these viruses upregulates a cellular protein called serine protease inhibitor Kazal (SPIK). (nih.gov)
  • Since our previous studies have shown that SPIK is an inhibitor of serine protease-dependent apoptosis, it is hypothesized that the upregulation of SPIK caused by HBV and HCV replication leads to cell resistance to apoptosis. (nih.gov)
  • The evasion of apoptotic death by infected cells results in persistent viral replication and constant liver inflammation, which leads to gradual accumulation of genetic changes and eventual development of cancer. (nih.gov)
  • SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication. (asm.org)
  • Histone mimicry helps us to generate a framework for understanding how the virus interferes with gene expression in infected cells," Dr. Tarakhovsky explained to underscore how histone mimicry has created a new paradigm that explains how the accumulation of these proteins could attenuate the immune response and allow viral replication. (genengnews.com)
  • The E1 protein plays a role in multiple steps in the HCV replication cycle, including attachment to the host cell, endosome-lipid membrane fusion, and assembly. (uw.edu)
  • MicroRNAs (miRNAs) are endogenous 21-23 nt small non-coding RNA molecules that binding to a multiple of target mRNAs and functioning in the regulation of viral replication including the miRNA-mediated antiviral defense. (biomedcentral.com)
  • Furthermore, the miR-3470b mimic transfection significantly contributed to increase the BEFV N mRNA, G protein level and viral titer, respectively, whereas the miR-3470b inhibitor had the opposite effect on BEFV replication. (biomedcentral.com)
  • Moreover, the overexpression of MAVS or silencing of miR-3470b by its inhibitors suppressed BEFV replication, and knockdown of MAVS by small interfering RNA also promoted the replication of BEFV. (biomedcentral.com)
  • After screening an RNA-biased library using a peptide-displacement assay, we identify DMA-135 as a dose-dependent inhibitor of viral translation and replication with no significant toxicity in cell-based studies. (duke.edu)
  • We are now using the E5 protein as a scaffold to construct novel, small transmembrane proteins that modulate cell phenotype and virus replication by interacting with a variety of transmembrane target proteins. (yale.edu)
  • Bevirimat prevents this viral replication by specifically inhibiting cleavage of the capsid protein (CA) from the SP1 spacer protein. (xcessbio.com)
  • Replication of SARS-CoV-2, the virus responsible for COVID-19, depends on a series of interactions between viral proteins and different cellular partners such. (pasteur.fr)
  • Here we have characterized the deamination mechanisms of Apo3A on ssDNA and two reconstituted systems that represent HIV replication and DNA transcription. (ecolowood.com)
  • Advances in understanding the molecular biology of virus replication cycles and detailed three-dimensional structures of viral molecules have made it possible to create particular and effective antiviral drugs. (microbeonline.com)
  • The virus replication cycle or life cycle starts with the attachment of the virus to the host cell with the help of protein in the virus and host cell receptors. (microbeonline.com)
  • Afterward, replication and protein synthesis occur. (microbeonline.com)
  • Rather than killing or inactivating viruses, antiviral drugs focus on inhibiting viral replication by interfering with specific stages of the viral life cycle. (microbeonline.com)
  • Antiviral drugs block various stages of viral replication. (microbeonline.com)
  • Drugs that inhibit attachment and virus entry prevent all subsequent steps of the viral replication cycle and virus infection. (microbeonline.com)
  • Some antiviral drugs target DNA or RNA polymerase to inhibit DNA/RNA replication , e.g., viral DNA polymerase inhibitors, like acyclovir and tenofovir. (microbeonline.com)
  • The Gag polyprotein, and in particular its constituent nucleocapsid protein, NC, represents a prime target for antiretroviral inhibition. (nih.gov)
  • The discovery of modern pharmaceutical antiviral medicine frequently targets viral protease inhibition. (castanet.net)
  • Zinc functions as a natural viral protease inhibitor via direction inhibition of the protease active site. (castanet.net)
  • The second mechanism of antiviral activity is through inhibition of polymerase activity. (castanet.net)
  • It turns out that viruses have evolved histone-like proteins, "histone mimics," that undergo the same post-translational modifications as histones, and when concentrated in the cell nucleus they can distort gene regulation through competitive inhibition by tricking epigenetic regulators with their clever disguise. (genengnews.com)
  • Serpin-dependent mechanism of protease inhibition. (researchgate.net)
  • Immunomodulation at the level of NF-κB activation and inhibitors of NF-κB (IκB) degradation along with TNF-α inhibition will potentially result in a reduction in the cytokine storm and alleviate the severity of COVID-19. (springer.com)
  • We show that 4EBP1 is a critical regulator of the mitogen responsive RAS/ERK and PI3K/AKT pathways and a key transducer of resistance mechanisms that affect small molecule inhibition of these pathways, principally by attenuating their effects on cap-dependent translation. (biomedcentral.com)
  • It is believed to inhibit HIV by a novel mechanism, so-called maturation inhibition. (xcessbio.com)
  • This raises a fundamental question in biology as to how proteins are synthesized during periods of cellular stress and eIF4E inhibition. (researchcbs.ca)
  • Recently, we have found that combination of SAMT-247 formulated as a microbicide with a vaccine provided a high degree of protection from viral infection in a rhesus macaque model. (nih.gov)
  • The lentiviral protein Viral Infectivity Factor (Vif) counteracts the antiviral effects of host APOBEC3 (A3) proteins and contributes to persistent HIV infection. (nih.gov)
  • This appears to better to produce a local effect at the site of viral infection and inhibiting pathogenic inflammation created there. (castanet.net)
  • The in vivo anti-ZIKV study shows that the middle-dose (4.77 mg/kg/d) of ZFD-10 protected mice from ZIKV infection and the viral loads of the blood, liver, kidney and brain in the middle-dose and high-dose (9.54 mg/kg/d) were significantly reduced compared to those of the ZIKV control. (bvsalud.org)
  • The current results show that certain compounds are broad-spectrum inhibitors of ZIKV- and dengue virus (DENV)-infection while distinctive compounds are selective ZIKV inhibitors or selective DENV inhibitors. (bvsalud.org)
  • Moreover, compounds of 12, 17 and 18 are anti-ZIKV agents with the inhibitory activities to ZIKV NS5 RdRp while 12 doesn't inhibit DENV infection even though it is a DENV RdRp inhibitor, 17 is an active agent against DENV infection but is only a weak DENV NS5 RdRp inhibitor, and 28 is inactive against DENV infection and not a DENV NS5 RdRp inhibitor. (bvsalud.org)
  • This article reviews the mechanism of action, resistance, pharmacokinetics, and adverse effects of each of these classes, as well as current treatment guidelines for their use in adults and adolescents with HIV infection. (medscape.com)
  • Infection by either virus can cause chronic hepatitis, liver cirrhosis, and ultimately, liver cancer, despite the fact that no pathogenetic mechanisms are known which are shared by the two viruses. (nih.gov)
  • The aim of our study herein was to investigate the exact function of miR-3470b and its molecular mechanisms during BEFV infection. (biomedcentral.com)
  • Bovine ephemeral fever (BEF), known as "three day sickness", is an arthropod-borne and acute viral infection of cattle and water buffalo. (biomedcentral.com)
  • 2005 ). Herein, we review current literature on the effect of SARS-nCoV-2 infection on NF-κB activation and discuss the potential therapeutic role of inhibitors of this pathway in the treatment of COVID-19. (springer.com)
  • SUNLENCA, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations. (nih.gov)
  • So far, we have constructed artificial proteins that can drive the formation of human red blood cells and others that block infection by HIV. (yale.edu)
  • Here, we evaluated 6710 clinical and preclinical compounds targeting 2183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. (biorxiv.org)
  • The HIV genome also codes for protease (PR), an enzyme that acts later in infection by cutting long viral polyproteins into smaller, functional proteins. (easynotecards.com)
  • Proviral infection at the "site of the highest degree" was thought to be the mechanism of carcinogenesis, giving the first name to the gene found along this pathway as INT1. (chemdiv.com)
  • Interaction between the cellular protein eEF1A and the 3′-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis. (microbiologyresearch.org)
  • Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. (plos.org)
  • To this aim, the Keystone Symposia on Molecular and Cellular Biology hosted a conference focused on "Epigenetics and Human Disease: Progress from Mechanisms to Therapeutics" in Seattle at the end of January. (genengnews.com)
  • We discovered that the 44-amino acid transmembrane E5 protein of bovine papillomavirus transforms cells to tumorigenicity by binding to and activating the cellular platelet-derived growth factor receptor. (yale.edu)
  • We also showed that direct interactions involving specific transmembrane and juxtamembrane amino acids in the E5 protein and the PDGF ß receptor result in dimerization and trans-phosphorylation of the receptor, and recruitment of cellular signaling molecules into a signal transduction complex. (yale.edu)
  • Each Asimadoline miRNA is definitely involved in numerous cellular processes, such as development, differentiation, tumorigenesis, and viral illness. (portefeuillessac.com)
  • They represent the active complexes in cellular protein synthesis and are able to incorporate amino acids into polypeptides both in vivo and in vitro. (lookformedical.com)
  • Senior author James M. Cunningham, M.D., of Brigham and Women's Hospital and Harvard Medical School in Boston, and his colleagues discovered two cellular enzymes that the Ebola virus co-opts and uses to cut up one of the virus' surface proteins. (scienceblog.com)
  • Autophagy, an evolutionarily conserved cellular catabolic process, facilitates the recycling of damaged proteins and organ- elles (7). (pdfslide.net)
  • Plasminogen activator inhibitor type 2 (PAI-2), a serine pro- teinase inhibitor (SERPIN), originally was identi fi ed as an inhibitor of the urokinase-type plasminogen activator (uPA) involved in cellular invasion and tissue remodeling (10). (pdfslide.net)
  • These immune differences are reflected in varied immune responses, cellular subset composition, cytokine production, and cellular/humoral protein levels ( 3 , 4 , 6 , 7 ). (frontiersin.org)
  • β-Catenin is a fascinating protein with many important cellular and developmental functions. (chemdiv.com)
  • β -catenin has many binding partners that mediate a diverse set of cellular functions, and the protein probably acts as a 'hub' on which many cellular signaling networks impinge. (chemdiv.com)
  • Over the last several years, a class of small molecule inhibitors of the HIV nucleocapsid protein NCp7 have been developed based upon an S-acyl-2-mercaptobenzamide thioester (SAMT) scaffold. (nih.gov)
  • In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. (medscape.com)
  • Down-regulation of eIF2 by phosphorylation of its α-subunit is a highly conserved mechanism for inhibiting general protein synthesis under starvation and stress conditions in mammalian cells, and mediates gene-specific translational induction of GCN4 expression in yeast. (nih.gov)
  • In genetic screens aimed at understanding drug resistance mechanisms in chronic myeloid leukemia cells, inactivation of the cullin 3 adapter protein-encoding leucine zipper-like transcription regulator 1 ( LZTR1 ) gene led to enhanced mitogen-activated protein kinase (MAPK) pathway activity and reduced sensitivity to tyrosine kinase inhibitors. (nih.gov)
  • During previous coronavirus outbreaks, such as SARS-CoV and the Middle East Respiratory syndrome coronavirus (MERS-CoV), it was reported that viral proteins such as nsp1, nsp3a, nsp7a, spike, and nucleocapsid protein all caused excessive NF-κB activation, possibly contributing to severe disease and high case-fatality rate (DeDiego et al. (springer.com)
  • In this review we summarize recent research pertaining to potential pathogenic mechanisms of environmental exposures that may be involved in the development of SLE in humans and recommendations for new research to better understand environmental influences and gene-environment interactions in lupus. (nih.gov)
  • Nevertheless, in terms of pathology, the underlying pathogenic mechanisms of BEFV have not largely been elucidated. (biomedcentral.com)
  • Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. (lookformedical.com)
  • It was identified in a high-throughput chemical screen as inhibiting recognition of the nuclear localizing Human Immunodeficiency Virus 1 (HIV-1) integrase protein by the host heterodimeric importin (IMP) α/β1 complex, and has since been shown to bind directly to IMPα to induce conformational changes that prevent its normal function in mediating nuclear import of key viral and host proteins. (encyclopedia.pub)
  • Furthermore, ZFD-10 could protect ZIKV NS5 from thermal unfolding and aggregation and increase the Tagg value of ZIKV NS5 protein from 44.6 to 49.3 °C, while ZFD-10 dose-dependently inhibits ZIKV NS5 RdRp activity using in vitro RNA polymerase assays. (bvsalud.org)
  • Nonnucleoside inhibitors bind non-competitively to the polymerase or reverse transcriptase, impairing its function, e.g., nevirapine. (microbeonline.com)
  • In addition, the biogenesis of miRNA is definitely a multistep process involving numerous proteins, although the complete pathway remains to be elucidated. (portefeuillessac.com)
  • In search for a mechanism that would engage the cGAS-STING pathway in ageing, we considered aberrant mitochondrial DNA species," says Ablasser. (worldhealth.net)
  • Indeed, in microglia from old, but not young mice, DNA from mitochondria accumulated in the cell cytoplasm, suggesting a possible mechanism by which the cGAS-STING pathway contributes to inflammation in the ageing brain. (worldhealth.net)
  • Nussе and Varmus identified components of the Wnt/β-catenin pathway in 1982 in a study of oncogenic breast tumor viral diseases (MMTV) [1]. (chemdiv.com)
  • We have reconstituted in yeast cells the antagonism of PKR and other eIF2α kinases by viral inhibitors and we are using yeast and mammalian cell experiments, as well as biochemical assays and evolution studies, to identify the molecular determinants of eIF2α kinase regulation. (nih.gov)
  • But the molecular mechanism underlying HIV-1 uptake by mDCs has until now been elusive. (plos.org)
  • E1 is a type I transmembrane protein that has a molecular weight of 23 kDa and is 192 amino acids long. (uw.edu)
  • Accumulated knowledge about the tick saliva composition at the molecular level has revealed that serine protease inhibitors play a key role in the tick-host interact. (researchgate.net)
  • The molecular weight of proteins were 102, 88 and 80 kDa, so they were named α, β and γ-catenin. (chemdiv.com)
  • We design and synthesize new drug molecules that act as agonists or antagonists of G protein-coupled receptors (GPCRs). (nih.gov)
  • The gp120-induced mucus formation was clogged from the inhibitors of CXCR4 α7-nicotinic acetylcholine receptor (α7-nAChR) and γ-aminobutyric acid (GABA)AR but not the antagonists of CCR5 and epithelial growth element receptor (EGFR). (biongenex.com)
  • Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. (wikipedia.org)
  • The GTPase eEF2 functions in the elongation phase of protein synthesis to promote translocation of the tRNAs and mRNA on the ribosome following each round of peptide bond formation. (nih.gov)
  • eIF2 plays a pivotal role in the initiation of protein synthesis by delivering tRNAiMet to the ribosome, and also functions in recognition of the AUG start codon. (nih.gov)
  • Accordingly, eIF5A and its hypusine modification are required both in vivo and in vitro for the synthesis of proteins containing polyproline sequences. (nih.gov)
  • Together with Marat Yusupov we obtained the structure of eIF5A bound to the yeast 80S ribosome and we are characterizing translational control mechanisms that exploit the eIF5A-dependency for polyproline synthesis. (nih.gov)
  • SARS-CoV-2 uses a multipronged strategy to impede host protein synthesis. (asm.org)
  • Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA. (asm.org)
  • Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis. (lookformedical.com)
  • It inhibits protein synthesis by binding to RNA. (lookformedical.com)
  • It is an antineoplastic and antitrypanosomal agent and is used in research as an inhibitor of protein synthesis. (lookformedical.com)
  • Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. (researchcbs.ca)
  • The initial step of protein synthesis consists of the eukaryotic translation initiation factor 4E (eIF4E) binding to the 5' cap of mRNAs. (researchcbs.ca)
  • Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added. (medscape.com)
  • The Chemical Biology in Signaling Section develops new methods and tools to probe and modulate the function of cell surface proteins. (nih.gov)
  • The use of nanobodies, which enables targeting of a wide array of cell surface proteins, allows us to select the identity of the cell surface receptor(s) based on chemical and biological considerations. (nih.gov)
  • The VPS machinery drives viral budding by invaginating regions of the plasma membrane or vesicular membranes, where Gag is then processed to form a mature virion surrounded by a host-derived lipid envelope containing the viral Envelope (Env) protein. (nature.com)
  • In human immunodeficiency virus (HIV)-infected individuals, the level of the HIV envelope protein gp41 in brain tissue is correlated with neurological damage and dementia. (nih.gov)
  • Gangliosides are known to be incorporated into the viral envelope membrane during the process of viral particle budding and here we show that they serve as viral attachment factors: they are recognized and enable HIV-1 uptake by mDCs. (plos.org)
  • The core protein is the first protein to be translated from the HCV genome and together with the envelope glycoproteins (E1 and E2) comprise the three structural HCV proteins. (uw.edu)
  • The envelope glycoprotein E1 protein is a highly glycosylated transmembrane protein that tightly associates with the E2 glycoprotein to form the envelope glycoprotein E1-E2 heterodimer. (uw.edu)
  • Following endocytosis of the HCV particle, the acidic environment in the endosome stimulates conformational changes in E1 and E2, which generates fusion of the endosomal membrane with the viral envelope and release of the HCV RNA into the cytoplasm. (uw.edu)
  • In addition, most animal viruses have a lipid envelope with protein spike receptors for the attachment to the host cell surface. (microbeonline.com)
  • Drugs like enfuvirtide bind gp41 of the viral envelope and inhibit viral fusion with the host cell membrane. (microbeonline.com)
  • Severe presentations of COVID-19 such as severe pneumonia and acute respiratory distress syndrome (ARDS) have been associated with the post-viral activation and release of cytokine/chemokines which leads to a "cytokine storm" causing inflammatory response and destruction, mainly affecting the lungs. (springer.com)
  • NF-κB is a complex system of proteins present inactive in the cytoplasm along with inhibitory proteins that are known as inhibitors of NF-κB (IκBs). (springer.com)
  • These compounds could serve as scaffolds for the development of more potent and selective inhibitors of PV. (cdc.gov)
  • ChemDiv's Inhibitors of beta-Catenin Signaling Library contains 8,000 compounds. (chemdiv.com)
  • This library represents a selection of drug-like compounds aimed at modulating protein-protein interaction (PPI) of β-catenin with different proteins involved in significant physiological processes. (chemdiv.com)
  • Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). (wikipedia.org)
  • Strosberg AD, Kota S, Takahashi V, Snyder JK, Mousseau G. Core as a novel viral target for hepatitis C drugs. (uw.edu)
  • HBV vaccine available since 1982 uses recombinant DNA technology to express hepatitis B surface antigen (HBsAg)-a protein that forms viral-like nanoparticles-in yeast. (buyresearchchemicalss.net)
  • Excluded from this PA are targets and approaches already under extensive investigation by academia and the pharmaceutical sector, non-targeted random screening of potential inhibitors, and research on AIDS-associated opportunistic pathogens and malignancies. (nih.gov)
  • Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. (nih.gov)
  • Each class targets a different step in the viral life cycle as the virus infects a CD4 T lymphocyte or other target cell. (medscape.com)
  • The FightAIDS@Home team is working with the World Community Grid technical team to create a new sampling protocol, which will more closely predict the binding strengths of potential drugs to their HIV protein targets as determined in real-life experiments. (boinc-af.org)
  • These detailed studies establish enterovirus RNA structures as promising drug targets while revealing an approach and mechanism of action that should be broadly applicable to functional RNA targeting. (duke.edu)
  • Different serine protease inhibitors termed serpins, which are expressed in the cardiovascular system, can exert a fine-tuned regulation of protease activities. (researchgate.net)
  • Plasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. (researchgate.net)
  • Active serine proteases and their regulation by inhibitors in the circulating blood form the basis for both clot-formation and clot-solubilization cascades [6]. (researchgate.net)
  • Here we show that depletion of plasminogen activator inhibitor type 2 (PAI-2), a serine protease inhibitor, resulted in NLRP3- and ASC (apoptosis-associated Speck- like protein containing a C-terminal caspase recruitment domain) ‐ dependent caspase-1 activation and IL-1 β secretion in macrophages upon Toll-like receptor 2 (TLR2) and TLR4 engagement. (pdfslide.net)
  • Neuraminidase Inhibitors are chemically related antiviral medications that block the viral neuraminidase enzyme and have activity against both influenza A and B viruses. (cdc.gov)
  • Currently in Phase I trials for advanced B-cell lymphomas, Constellation's EZH2 inhibitor, CPI-1205, promotes transcription by binding to the active site of EZH2, an enzyme that normally represses transcription by "writing" methyl groups to a particular lysine residue on the histone H3 tail. (genengnews.com)
  • The scientists applied broad-spectrum enzyme inhibitors to mammalian cells before exposing them to Ebola virus. (scienceblog.com)
  • The authors write, "Further investigation of the antiviral efficacy of [enzyme] inhibitors may…be warranted. (scienceblog.com)
  • Scientists at NIH's National Institute of Allergy and Infectious Diseases (NIAID), along with collaborators at the Veterinary Laboratories Agency in Scotland, genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby allowing it to diffuse freely in the fluid outside the cells. (nih.gov)
  • HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4 + T lymphocytes. (plos.org)
  • HIV can enter DCs via a non-infectious endocytic mechanism and trick them into passing infectious virus on to bystander CD4 + T cells. (plos.org)
  • Scientists have known that viral proteins from infectious diseases like Zika, dengue, yellow fever, and influenza accumulate in the nucleus of infected cells, but they did not know what purpose those proteins served. (genengnews.com)
  • The virus's nucleic acid instructs the host cell to produce viral components, which leads to an infectious virus. (microbeonline.com)
  • They are often used in combination with NS5A inhibitors. (wikipedia.org)
  • Inactivation of LZTR1 led to decreased ubiquitination and enhanced plasma membrane localization of endogenous KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). (nih.gov)
  • As a component of the nucleocapsid structure, the mature core protein has properties that promote binding to the host-derived lipid membrane and HCV RNA. (uw.edu)
  • Then fusion of viral particles with the host cell membrane is followed by virus entry inside the host cell. (microbeonline.com)
  • Membrane fusion inhibitor drugs target mainly the enveloped viruses. (microbeonline.com)
  • Using mass spectrometry approaches, we have examined the mechanism of Gag inactivation both in vitro and in treated cells. (nih.gov)
  • We have used mass spectrometry to investigate the mechanism of viral inactivation of NC and Gag by SAMT, identifying multiple sites of covalent modification that resulted from SAMT reaction. (nih.gov)
  • The viral protein NSP1 acts as a ribosome gatekeeper for shutting down host translation and fostering SARS-CoV-2 translation. (asm.org)
  • These inhibitors covalently modify the zinc-binding domains of NCp7 in vitro and in cells. (nih.gov)
  • The PABP-specific translation inhibitor PABP-interacting protein 2 (Paip2) interferes with the DENV 3′UTR-PABP interaction, and in vitro translation of DENV reporter RNAs in baby hamster kidney cell extracts is inhibited by Paip2 in a dose-dependent manner. (microbiologyresearch.org)
  • Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro . (jneurosci.org)
  • Results: The results showed that a low concentration of HCP1 decreased viral titer and viral load in BHK-21 and PK-15 cells, and 5μM HCP1 significantly decreased the expression of SVA VP2 protein. (eurekaselect.com)
  • Furthermore the Apo3A-based viral restriction system may have a genomic cost as Apo3A is able to deaminate dsDNA undergoing transcription. (ecolowood.com)
  • Combined biochemical, cell biological and structural studies reveal that disruption of Vif E3 assembly inhibited A3 ubiquitination but was not sufficient to restore its packaging into viral particles and antiviral activity. (nih.gov)
  • So, the drugs targeted against viruses must be selectively toxic to inhibit the viral particles without adversely affecting the host cell. (microbeonline.com)
  • BET bromodomain inhibitors (BBIs) bind to the acetyl-lysine binding pockets of proteins within the BET bromodomain subfamily (BRD2, BRD3, BRD4, and BRDT), and they interfere with the protein's ability to perform its normal function as an epigenetic reader by blocking its interaction with acetylated histone lysine residues. (genengnews.com)
  • Like protease inhibitors, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV polyprotein precursor, called gag. (xcessbio.com)
  • Additionally, the target association between miR-3470b and mitochondrial antiviral signaling protein (MAVS) was predicted by target gene prediction tools and further validated using a dual-luciferase reporter assay, and the expression of MAVS mRNA and protein levels was negatively associated with miR-3470b levels. (biomedcentral.com)
  • We developed a protein fragment complementation (PCA) assay that can accurately measure the status of the eIF4E-eIF4G interaction in cells and quantify the signalling flux through the RAS/ERK and PI3K/AKT pathways regulating eIF4F assembly. (biomedcentral.com)
  • The HCV core is a structural protein that aggregates to form the viral capsid, a spherical structure that surrounds and protects the viral genomic RNA. (uw.edu)
  • The N-terminal region of the core proteins bind to the HCV genomic RNA. (uw.edu)
  • TLR2 or TLR4 agonist induced PAI-2 expression, which subsequently stabi- lized the autophagic protein Beclin 1 to promote autophagy, result- ing in decreases in mitochondrial reactive oxygen species, NLRP3 protein level, and pro - IL-1 β processing. (pdfslide.net)
  • Macrophages treated with an autophagy inhibitor or with the deletion of several autophagic components, including Atg16L1, Beclin 1, and LC3, induced greater caspase-1 activation and IL- 1 β secretion in response to LPS or LPS plus an NLRP3 agonist (8, 9). (pdfslide.net)
  • These data strongly suggest that the NLRP3 in fl amma- some activity is negatively regulated by autophagy, but the un- derlying mechanism is poorly understood. (pdfslide.net)
  • We have identified a novel mechanism of action for this class of inhibitors that involves covalent modification of Gag, both within and outside NC. (nih.gov)
  • Studies of antizyme inhibitor (AZIN1) translational control revealed a novel mechanism of translation start site selection involving ribosome queuing. (nih.gov)
  • The adamantanes target the M2 ion channel protein of influenza A viruses. (cdc.gov)
  • Antigen-presenting cells such as dendritic cells (DCs) are required to combat infections, but viruses including HIV have evolved strategies to evade their anti-viral activity. (plos.org)
  • These findings suggest a possibility by which HBV and HCV, two very different viruses, can share a common mechanism in provoking liver disease and cancer. (nih.gov)
  • This new research sheds light on the mechanism Ebola virus uses to enter cells," notes NIAID Director Anthony S. Fauci, M.D. "These findings raise the possibility of a broad-spectrum antiviral therapy that could be effective against multiple hemorrhagic fever viruses. (scienceblog.com)
  • Towards this end we devise new chemical approaches to connect synthetic molecules and recombinantly expressed proteins to create hybrid conjugates with unique properties. (nih.gov)
  • Therefore, recognition of molecules that can specifically modulate each step will help understand the mechanism of gene suppression. (portefeuillessac.com)
  • In fl ammasomes, multiple protein complexes contain- ing NLR proteins or AIM2, mediate caspase-1 activation leading to the processing of the proin fl ammatory cytokines IL-1 β and IL- 18 (3). (pdfslide.net)
  • RSV induced phosphorylation of the actin binding protein cortactin in a PKD-dependent manner. (nih.gov)
  • We are studying how the function of eukaryotic translation initiation factor 2 (eIF2) is regulated by phosphorylation, focusing on determinants of substrate recognition by the eIF2α protein kinases and the structure and regulation of these enzymes. (nih.gov)
  • We are also studying the mechanisms by which phosphorylation of eIF2α enhances translation of mRNAs encoding key stress responsive factors. (nih.gov)
  • Previous work identified the stem loop II structure of the EV71 internal ribosomal entry site as vital to viral translation and a potential target. (duke.edu)
  • It is composed of the 16S RIBOSOMAL RNA and about 23 different RIBOSOMAL PROTEINS. (lookformedical.com)
  • Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. (lookformedical.com)
  • The wealth of existing knowledge regarding the design and in vivo pharmacology of these inhibitors may facilitate development of an anti-Ebola-virus therapy. (scienceblog.com)
  • SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein. (asm.org)
  • Recent studies also suggest the E1 protein interacts with several other viral proteins to coordinate the HCV assembly process. (uw.edu)
  • eIF4E interacts directly with the 5′ cap structure of mRNA, whilst the eIF4A helicase unwinds the secondary structure present in the 5′UTR of mRNAs and eIF4G, which interacts with both eIF4A and eIF4E, recruits eIF3 and interacts with PABP (polyadenylate-binding protein) [ 4 ]. (biomedcentral.com)
  • These findings demonstrated that receptor tyrosine kinases can be activated by proteins that do not resemble their normal ligands and that specific transmembrane interactions can drive receptor activation and tumor formation. (yale.edu)
  • PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). (researchgate.net)
  • The D3 domain corresponds to the extreme C-terminal region that is cleaved and therefore is absent in the mature capsid protein. (uw.edu)
  • Current treatments are limited to targeting the herpesvirus DNA polymerases, but with emerging viral resistance and little efficacy against the oncogenic herpesviruses, there is an urgent need for new antiviral strategies. (nature.com)
  • These findings highlight the importance of highly efficacious direct inhibitors of eIF4E and eIF4F assembly, which could potentially target a wide spectrum of tumours containing differing mutations that effect these pathways and which confer chemo-resistance. (biomedcentral.com)
  • Poly(A)-binding protein (PABP) is a key player in mRNA circularization and translation initiation of polyadenylated mRNAs. (microbiologyresearch.org)
  • Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. (medscape.com)
  • SARS-CoV-2 Omicron Variant: ACE2 Binding, Cryo-EM Structure of Spike Protein-ACE2 Complex and Antibody Evasion. (asm.org)
  • Structural impact on SARS-CoV-2 spike protein by D614G substitution. (asm.org)
  • Drugs of this category target host receptors, co-receptors, or viral spike proteins. (microbeonline.com)
  • Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects," said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session. (medscape.com)
  • The efficacy and mechanism of hydroxyurea in the treatment of atherosclerosis have rarely been reported. (thno.org)
  • The goal of this study was to investigate the efficacy of hydroxyurea in high-fat diet-fed ApoE -/- mice against atherosclerosis and examine the possible mechanism underlying treatment outcomes. (thno.org)
  • Our findings show an expanded translation mechanism for PABP, binding to a viral RNA lacking a terminal poly(A) tail. (microbiologyresearch.org)
  • Poly(A)-binding protein is differentially required for translation mediated by viral internal ribosome entry sites. (microbiologyresearch.org)
  • Structural, biophysical, and biochemical characterization support an allosteric mechanism in which DMA-135 induces a conformational change in the RNA structure that stabilizes a ternary complex with the AUF1 protein, thus repressing translation. (duke.edu)
  • mRNA polyadenylate-binding protein: gene isolation and sequencing and identification of a ribonucleoprotein consensus sequence. (microbiologyresearch.org)
  • Our study indicates that 2 types of brain damage occur in prion diseases: abnormal prion protein plaques that destroy brain blood vessels and displace brain tissue, and abnormal prion protein without plaques that leads to the sponge-like damage to nerve cells," says lead author Dr. Bruce Chesebro, chief of the Laboratory of Persistent Viral Diseases at NIAID's Rocky Mountain Laboratories. (nih.gov)
  • The balance between proteases and protease inhibitors plays a critical role in tissue remodeling during cardiovascular diseases. (researchgate.net)
  • Finding medical countermeasures for viral hemorrhagic fevers is a global public health priority because not only do these diseases occur naturally but they also have the potential to be unleashed by bioterrorists," says NIH Director Elias A. Zerhouni, M.D. (scienceblog.com)
  • In humans, viral infections vary from self-resolving to acute, fatal diseases. (microbeonline.com)
  • Therefore, it is much more difficult for drugs to combat viral diseases effectively. (microbeonline.com)
  • Abstract Argonaute (AGO) proteins are the important component of the RNA interference machinery that suppresses gene manifestation by forming an RNA-induced silencing complex (RISC) with microRNAs (miRNAs). (portefeuillessac.com)
  • The research found that activating the STING protein triggers specific patterns of gene activity in microglia, the brain's first-line-of-defense immune cells. (worldhealth.net)
  • The roles of b-catenin are 'classically' defined: as an adhesion protein and as a signaling protein, transducing extracellular signals to the nucleus to modify gene expression. (chemdiv.com)
  • Recent research has advanced our understanding of mechanisms involved in the loss of tolerance and development of a chronic state of inflammation, with work involving the role of apoptosis in the generation and clearance of immunogenic intracellular self-antigens, adjuvant or bystander effects, toll-like receptors (TLRs) and innate immunity, and abnormal DNA methylation. (nih.gov)
  • Overexpression of Caspase 8 induces apoptosis, which can be blocked by inhibitors specific for the ICE family. (thermofisher.com)
  • The encircled active site, unique to NS5B, is contained within the palm structure of the protein. (wikipedia.org)
  • SARS-CoV-2 Nsp5 Demonstrates Two Distinct Mechanisms Targeting RIG-I and MAVS To Evade the Innate Immune Response. (asm.org)
  • When activated, cGAS/STING triggers an immune response to defend against viral and bacterial infections. (worldhealth.net)
  • Although antiretroviral therapy to treat HIV has advanced, there remains a critical need for new therapeutics, especially those targeted at resistant viral strains. (nih.gov)