A5010959513- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- interferon and immune responses
- Mosquito-borne diseases and control
- COVID-19 Clinical Research Studies
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Plant Virus Research Studies
- RNA and protein synthesis mechanisms
- Animal Disease Management and Epidemiology
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Viral Infections and Outbreaks Research
- Vector-Borne Animal Diseases
- Respiratory viral infections research
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Virology and Viral Diseases
- Long-Term Effects of COVID-19
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- RNA regulation and disease
Leiden University Medical Center
2016-2025
Lomonosov Moscow State University
2013
Institute of Macromolecular Chemistry
2012
European Molecular Biology Laboratory
2009
Pennsylvania State University
2009
Architecture et Fonction des Macromolécules Biologiques
2004
Centre National de la Recherche Scientifique
2004
Science Applications International Corporation (United States)
2001
National Cancer Institute
2001
Leiden University
1991-2000
During the summer of 2012, in Jeddah, Saudi Arabia, a hitherto unknown coronavirus (CoV) was isolated from sputum patient with acute pneumonia and renal failure (1, 2). The isolate provisionally called human Erasmus Medical Center (EMC) (3). Shortly thereafter, September same type virus, named England 1, recovered severe respiratory illness who had been transferred Gulf region Middle East to London, United Kingdom (4) (GenBank accession no. KC164505.2). onset new disease traced back an even...
Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV), replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified cell membranes. Membrane structures supporting viral synthesis range from distinct spherular membrane invaginations to more elaborate webs packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, exact role remain be defined. Poorly characterized...
ABSTRACT A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, organization, expression strategy of HCoV-EMC/2012 its relation known coronaviruses. The contains 30,119 nucleotides at least 10 predicted open reading frames, 9 which are to be expressed nested set seven subgenomic mRNAs. Phylogenetic analysis replicase gene coronaviruses completely sequenced genomes showed that...
A novel coronavirus is the causative agent of current epidemic severe acute respiratory syndrome (SARS). Coronaviruses are exceptionally large RNA viruses and employ complex regulatory mechanisms to express their genomes. Here, we determined sequence SARS (SARS-CoV), isolate Frankfurt 1, characterized key elements protein functions involved in viral genome expression. Important mechanisms, such as (discontinuous) synthesis eight subgenomic mRNAs, ribosomal frameshifting post-translational...
Increasing the intracellular Zn2+ concentration with zinc-ionophores like pyrithione (PT) can efficiently impair replication of a variety RNA viruses, including poliovirus and influenza virus. For some viruses this effect has been attributed to interference viral polyprotein processing. In study we demonstrate that combination PT at low concentrations (2 µM 2 PT) inhibits SARS-coronavirus (SARS-CoV) equine arteritis virus (EAV) in cell culture. The synthesis these two distantly related...
ABSTRACT Coronaviruses can cause respiratory and enteric disease in a wide variety of human animal hosts. The 2003 outbreak severe acute syndrome (SARS) first demonstrated the potentially lethal consequences zoonotic coronavirus infections humans. In 2012, similar previously unknown emerged, Middle East (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise number cases being recorded recent months. MERS fatality rate ∼30% is alarmingly high,...
Significance The 2003 severe acute respiratory syndrome (SARS) epidemic and recent emergence of Middle East highlight the potential lethality zoonotic coronavirus infections in humans. No specific antiviral treatment options are available. Coronaviruses possess largest known RNA virus genomes encode a complex replication machinery consisting 16 viral nonstructural proteins (nsps). Our study reveals that SARS-coronavirus polymerase (nsp12) needs to associate with nsp7 nsp8 activate its...
The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end 2019 from Chinese province Hubei and its subsequent pandemic spread highlight importance understanding full molecular details infection pathogenesis. Here, we compared a variety replication features SARS-CoV-2 SARS-CoV analysed cytopathology caused by two closely related viruses in commonly used Vero E6 cell line. Compared to SARS-CoV, generated higher levels intracellular viral RNA, but...
The main protease of coronaviruses and the 3C enteroviruses share a similar active-site architecture unique requirement for glutamine in P1 position substrate. Because their specificity essential role viral polyprotein processing, these proteases are suitable targets development antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, enteroviruses, we pursued structure-based design peptidomimetic α-ketoamides as inhibitors...
ABSTRACT The RNA replication complexes of mammalian positive-stranded viruses are generally associated with (modified) intracellular membranes, a feature thought to be important for creating an environment suitable viral synthesis, recruitment host components, and possibly evasion defense mechanisms. Here, using panel replicase-specific antisera, we have analyzed the earlier stages severe acute respiratory syndrome coronavirus (SARS-CoV) infection in Vero E6 cells, particular focusing on...
Coronavirus genome replication is associated with virus-induced cytosolic double-membrane vesicles, which may provide a tailored microenvironment for viral RNA synthesis in the infected cell. However, it unclear how newly synthesized genomes and messenger RNAs can travel from these sealed compartments to cytosol ensure their translation assembly of progeny virions. In this study, we used cellular cryo-electron microscopy visualize molecular pore complex that spans both membranes vesicle...
Severe acute respiratory syndrome coronavirus (SARS-CoV), a newly identified group 2 coronavirus, is the causative agent of severe syndrome, life-threatening form pneumonia in humans. Coronavirus replication and transcription are highly specialized processes cytoplasmic RNA synthesis that localize to virus-induced membrane structures were recently proposed involve complex enzymatic machinery that, besides RNA-dependent polymerase, helicase, protease activities, also involves series...
Zoonotic coronavirus (CoV) infections, such as those responsible for the current severe acute respiratory syndrome-CoV 2 (SARS-CoV-2) pandemic, cause grave international public health concern. In infected cells, CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into viral replication organelle (RO). Although double-membrane vesicles (DMVs) appear to be a pan-CoV RO element, studies date describe an assortment of additional...
SARS-coronavirus (SARS-CoV) genome expression depends on the synthesis of a set mRNAs, which presumably are capped at their 5' end and direct all viral proteins in infected cell. Sixteen non-structural (nsp1 to nsp16) constitute an unusually large replicase complex, includes two methyltransferases putatively involved mRNA cap formation. The S-adenosyl-L-methionine (AdoMet)-dependent (guanine-N7)-methyltransferase (N7-MTase) activity was recently attributed nsp14, whereas nsp16 has been...
The nucleotide sequence of the genome equine arteritis virus (EAV) was determined from a set overlapping cDNA clones and found to contain eight open reading frames (ORFs). ORFs 2 through 7 are expressed six 3'-coterminal subgenomic mRNAs, which transcribed 3'-terminal quarter viral genome. A number these predicted encode structural EAV proteins. organization expression 3' part remarkably similar those coronaviruses toroviruses. 5'-terminal three-quarters putative polymerase gene, also shares...