A5028520054- Influenza Virus Research Studies
- Respiratory viral infections research
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Virology and Viral Diseases
- Animal Disease Management and Epidemiology
- Neonatal Respiratory Health Research
- Animal Virus Infections Studies
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
- Congenital Diaphragmatic Hernia Studies
- Pneumonia and Respiratory Infections
- Ubiquitin and proteasome pathways
- Diabetes and associated disorders
- Neonatal Health and Biochemistry
- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Virus-based gene therapy research
- Respiratory Support and Mechanisms
Philipps University of Marburg
2014-2024
Institute of Virology of the Slovak Academy of Sciences
2014-2023
The novel emerged SARS-CoV-2 has rapidly spread around the world causing acute infection of respiratory tract (COVID-19) that can result in severe disease and lethality. For to enter cells, its surface glycoprotein spike (S) must be cleaved at two different sites by host cell proteases, which therefore represent potential drug targets. In present study, we show S proprotein convertase furin S1/S2 site transmembrane serine protease 2 (TMPRSS2) S2′ site. We demonstrate TMPRSS2 is essential for...
Influenza A viruses (IAV) and influenza B (IBV) cause significant morbidity mortality during seasonal outbreaks. Cleavage of the viral surface glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion essential virus infectivity. Inhibition relevant provides promising therapeutic approach that may avoid development drug resistance. HA most cleaved at monobasic cleavage site, number have been shown to cleave in vitro . This study demonstrates transmembrane...
ABSTRACT Proteolytic cleavage of the influenza virus surface glycoprotein hemagglutinin (HA) by host cell proteases is crucial for infectivity and spread. The HAT (human airway trypsin-like protease) TMPRSS2 (transmembrane protease serine S1 member 2) known to be present in human airways were previously identified as that cleave HA. We studied subcellular localization HA inhibition seasonal A/Memphis/14/96 (H1N1) pandemic A/Hamburg/5/2009 MDCK cells express under doxycycline-induced...
ABSTRACT Cleavage of the hemagglutinin (HA) by host proteases is essential for infectivity influenza viruses. Here, we analyzed role serine protease TMPRSS2, which activates HA in human respiratory tract, pathogenesis a mouse model. Replication H7N9 isolate A/Anhui/1/13 and H1N1 H3N2 viruses was compared TMPRSS2 knockout ( −/− ) wild-type (WT) mice. Knockout expression inhibited virus replication explants murine tracheas, bronchi, lungs. also strongly suppressed airway mice, while only...
TMPRSS2 (transmembrane serine proteinase 2) is a multidomain type II transmembrane protease that cleaves the surface glycoprotein HA (haemagglutinin) of influenza viruses with monobasic cleavage site, which prerequisite for virus fusion and propagation. Furthermore, it activates protein F human metapneumovirus spike S SARS-CoV (severe acute respiratory syndrome coronavirus). Increased expression was also described in several tumour entities. Therefore emerged as potential target drug design....
Influenza A viruses of the subtype H9N2 circulate worldwide and have become highly prevalent in poultry many countries. Moreover, they are occasionally transmitted to humans, raising concern about their pandemic potential. virus infectivity requires cleavage surface glycoprotein hemagglutinin (HA) at a distinct site by host cell proteases. vary remarkably amino acid sequence site, isolates from Asia Middle East possess multibasic motifs R-S-S-R R-S-R-R, but not activated furin. Here, we...
Abstract In December 2019, a novel coronavirus named SARS-CoV-2 first reported in Wuhan, China, emerged and rapidly spread to numerous other countries globally, causing the current pandemic. causes acute infection of respiratory tract (COVID-19) that can result severe disease lethality. Currently, there is no approved antiviral drug for treating COVID-19 patients an urgent need specific therapies vaccines. order enter cells, its surface glycoprotein spike (S) must be cleaved at two different...
Influenza A viruses constitute a major and ongoing global public health concern. Current antiviral strategies target viral gene products; however, the emergence of drug-resistant highlights need for novel approaches. Cleavage influenza virus hemagglutinin (HA) by host cell proteases is crucial infectivity therefore presents potential drug target. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded-DNA-like antisense agents that readily enter cells can act as...
Trophic functions for macrophages are emerging as key mediators of developmental processes, including bone, vessel, and mammary gland development. Yolk sac-derived mature in the distal lung shortly after birth. Myeloid-lineage recruited to activated under pathological conditions. These conditions include bronchopulmonary dysplasia (BPD), a common complication preterm birth characterized by stunted development, where formation alveoli is blocked. No study has addressed causal roles immune...
Gram-negative bacteria naturally secrete nano-sized outer membrane vesicles (OMVs), which are important mediators of communication and pathogenesis. OMV uptake by host cells activates TLR signalling via transported PAMPs. As resident immune cells, alveolar macrophages located at the air-tissue interface where they comprise first line defence against inhaled microorganisms particles. To date, little is known about interplay between OMVs from pathogenic bacteria. The response to underlying...
The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with carboxypeptidase angiotensin-converting enzyme (ACE2), cell surface protein serves as an entry receptor some coronaviruses. Here, by using activity assays, we determine ACE2 increases enzymatic in non-catalytic manner....
Cleavage of influenza virus hemagglutinin (HA) by host proteases is essential for infectivity. HA most A and B (IAV/IBV) viruses cleaved at a monobasic motif trypsin-like proteases. Previous studies have reported that transmembrane serine protease 2 (TMPRSS2) activation H7N9 H1N1pdm IAV in mice but H3N2 IBV independent TMPRSS2 carried out as-yet-undetermined protease(s). Here, to identify additional H3 IAV- IBV-activating proteases, we used RNA-Seq investigate the repertoire murine lower...
Abstract The activation of viral glycoproteins by the host protease furin is an essential step in replication numerous pathogenic viruses. Thus, effective inhibitors could serve as broad‐spectrum antiviral drugs. A crystal structure inhibitory hexapeptide derivative complex with served template for rational design various types new cyclic inhibitors. Most prepared derivatives are relatively potent inhibition constants low nanomolar or even sub‐nanomolar range. For seven structures be...
Cleavage of the influenza A virus (IAV) hemagglutinin (HA) by host proteases is indispensable for replication. Most IAVs possess a monobasic HA cleavage site cleaved trypsin-like proteases. Previously, transmembrane protease TMPRSS2 was shown to be essential proteolytic activation IAV subtypes H1, H2, H7, and H10 in mice. In contrast, additional are involved certain H3 IAVs, indicating that HAs with sites can differ their sensitivity Here, we investigated role avian H1 H11 H14 H16 human...
Abstract Certain corona- and influenza viruses utilize type II transmembrane serine proteases for cell entry, making these enzymes potential drug targets the treatment of viral respiratory infections. In this study, cytotoxicity inhibitory effects seven matriptase/TMPRSS2 inhibitors (MI-21, MI-463, MI-472, MI-485, MI-1900, MI-1903, MI-1904) on cytochrome P450 were evaluated using fluorometric assays. Additionally, their antiviral activity against A virus subtypes H1N1 H9N2 was assessed. The...
ABSTRACT Pigs are important natural hosts of influenza A viruses, and due to their susceptibility swine, avian, human they may serve as intermediate supporting adaptation genetic reassortment. Cleavage the virus surface glycoprotein hemagglutinin (HA) by host cell proteases is essential for viral infectivity. Most including swine activated at a monobasic HA cleavage site, we previously identified TMPRSS2 HAT be relevant present in airways. We investigated proteolytic activation viruses...
Abstract The proprotein convertase furin is a potential target for drug design, especially the inhibition of furin‐dependent virus replication. All effective synthetic inhibitors identified thus far are multibasic compounds; highest potency was found our previously developed inhibitor 4‐(guanidinomethyl)phenylacetyl‐Arg‐Tle‐Arg‐4‐amidinobenzylamide (MI‐1148). An initial study in mice revealed narrow therapeutic range this tetrabasic compound, while significantly reduced toxicity observed...