Publications by authors named "Sheli Radoshitzky"

is a family for ambisense RNA viruses with genomes of about 10.5 kb that infect mammals, snakes, and fish. The arenavirid genome consists of two or three single-stranded RNA segments and encodes a nucleoprotein (NP), a glycoprotein (GP) and a large (L) protein containing RNA-directed RNA polymerase (RdRP) domains; some arenavirids encode a zinc-binding protein (Z).

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  • In April 2023, the International Committee on Taxonomy of Viruses (ICTV) approved changes to the phylum's classification during their annual vote.
  • The update included the addition of one new family, 14 new genera, and 140 new species.
  • Additionally, the taxonomy featured the renaming of two genera and 538 species, along with the removal of one species and the abolition of four others.
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Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as a potent inhibitor of viral RNA-dependent RNA polymerases. Remdesivir and GS-441524 have antiviral activity against multiple RNA viruses.

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  • * It was expanded to include two new families, 41 new genera, and 98 new species, along with reclassifications for 349 species.
  • * The article details the updated taxonomy of Negarnaviricota, including corrections of misspelled names for seven species.
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Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus genome sequence information is available from clinical samples, reverse-genetics systems can be used to generate virus stocks de novo to initiate MCM development. In this study, we developed a reverse-genetics system for natural isolates of Ebola virus (EBOV) variants Makona, Tumba, and Ituri, which have been challenging to obtain.

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Article Synopsis
  • - In March 2021, the ICTV updated the phylum Negarnaviricota by officially ratifying new taxonomy changes.
  • - The revision included the addition of four families, three subfamilies, 42 genera, and 200 species, along with several renaming and abolishing of species.
  • - This article outlines the newly accepted taxonomic structure of Negarnaviricota following the ICTV's decisions.
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Simian hemorrhagic fever virus (SHFV) causes acute, lethal disease in macaques. We developed a single-plasmid cDNA-launch infectious clone of SHFV (rSHFV) and modified the clone to rescue an enhanced green fluorescent protein-expressing rSHFV-eGFP that can be used for rapid and quantitative detection of infection. SHFV has a narrow cell tropism in vitro, with only the grivet MA-104 cell line and a few other grivet cell lines being susceptible to virion entry and permissive to infection.

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Ebola virus (EBOV), a member of the mononegaviral family Filoviridae, causes severe disease associated with high lethality in humans. Despite enormous progress in development of EBOV medical countermeasures, no anti-EBOV treatment has been approved. We designed an immunotoxin in which a single-chain variable region fragment of the EBOV glycoprotein-specific monoclonal antibody 6D8 was fused to the effector domains of Pseudomonas aeruginosa exotoxin A (PE38).

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Emerging infectious diseases like those caused by arboviruses such as Venezuelan equine encephalitis virus (VEEV) pose a serious threat to public health systems. Development of medical countermeasures against emerging infectious diseases are of utmost importance. In this work, an acrylate and vinyl sulfone-based chemical series was investigated as promising starting scaffolds against VEEV and as inhibitors of the cysteine protease domain of VEEV's nonstructural protein 2 (nsP2).

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Article Synopsis
  • In March 2020, the International Committee on Taxonomy of Viruses (ICTV) made updates to the taxonomic classification of the phylum Negarnaviricota.
  • The revisions included adding 20 new genera, deleting 2, moving 1, and renaming 3 at the genus level, along with significant changes at the species level, such as adding 160 species.
  • The article provides the latest accepted taxonomy for Negarnaviricota as ratified by the ICTV.
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Article Synopsis
  • * Despite these findings, there are still major challenges in enhancing outcomes for acute Ebola infections and for patients who survive.
  • * Future efforts should focus on improving treatment strategies for severe cases, addressing viral persistence, optimizing post-exposure prevention, and exploring the potential of small-molecule antivirals in combination with existing therapies.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019. The virus rapidly spread globally, resulting in a public-health crisis including more than one million cases and tens of thousands of deaths. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected formalin fixed paraffin embedded (FFPE) cell pellets.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. The virus rapidly spread globally, resulting in a public health crisis including almost 5 million cases and 323,256 deaths as of May 21, 2020. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected FFPE cell pellets.

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All viruses balance interactions between cellular machinery co-opted to support replication and host factors deployed to halt the infection. We use gene correlation analysis to perform an unbiased screen for host factors involved in influenza A virus (FLUAV) infection. Our screen identifies the cellular factor epidermal growth factor receptor pathway substrate 8 (EPS8) as the highest confidence pro-viral candidate.

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Filoviridae currently includes five official and one proposed genera. Genus Ebolavirus includes five established and one proposed ebolavirus species for Bombali virus (BOMV), Bundibugyo virus (BDBV), Ebola virus (EBOV), Reston virus (RESTV), Sudan virus (SUDV) and Taï Forest virus (TAFV), and genus Marburgvirus includes a single species for Marburg virus (MARV) and Ravn virus (RAVV). Ebola virus (EBOV) has emerged as a significant public health concern since the 2013-2016 Ebola Virus Disease outbreak in Western Africa.

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Members of the family Arenaviridae produce enveloped virions containing genomes consisting of two or three single-stranded RNA segments totalling about 10.5 kb. Arenaviruses can infect mammals, including humans and other primates, snakes, and fish.

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  • In 2012, the Bas-Congo virus (BASV) was identified in a Congolese patient, but the lack of a replicating isolate has made it difficult to confirm its status as a human pathogen.
  • Subsequent discoveries of related viruses, EKV-1 and EKV-2, in Nigeria further complicate the situation as no isolates were obtained, but phylogenetic analysis groups them with BASV.
  • Research using recombinant viruses shows that tibrovirus glycoproteins can enter various cells, but many cell types appear resistant to infection, indicating that results from these surrogate systems may not reliably predict human infections.
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  • * A total of 11 new genera and 77 new species were also added, while one species was deleted and two species were merged.
  • * The article provides the revised taxonomy of Bunyavirales as recognized by the International Committee on Taxonomy of Viruses (ICTV).
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In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

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The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (phyla to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV's official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world, and therefore, have limited use for ICTV-devised taxa.

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Ebola virus (EBOV) disease is a viral hemorrhagic fever with a high case-fatality rate in humans. This disease is caused by four members of the filoviral genus , including EBOV. The natural hosts reservoirs of ebolaviruses remain to be identified.

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Lassa virus (LASV), a mammarenavirus, infects an estimated 100,000⁻300,000 individuals yearly in western Africa and frequently causes lethal disease. Currently, no LASV-specific antivirals or vaccines are commercially available for prevention or treatment of Lassa fever, the disease caused by LASV. The development of medical countermeasure screening platforms is a crucial step to yield licensable products.

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Sexual transmission of filoviruses was first reported in 1968 after an outbreak of Marburg virus (MARV) disease and recently caused flare-ups of Ebola virus disease in the 2013-2016 outbreak. How filoviruses establish testicular persistence and are shed in semen remain unknown. We discovered that persistent MARV infection of seminiferous tubules, an immune-privileged site that harbors sperm production, is a relatively common event in crab-eating macaques that survived infection after antiviral treatment.

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Article Synopsis
  • Several arenaviruses are linked to severe hemorrhagic fever in humans, prompting the need for effective countermeasures.
  • Utilizing an unbiased proteomic approach, researchers identified DDX3, a RNA-helicase, as a key protein interacting with arenavirus nucleoprotein (NP).
  • The study revealed that DDX3 deficiency hinders the replication of both Old and New World arenaviruses, suggesting it could be a promising target for new therapies against these dangerous viruses.
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