The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding

Tarbouriech, Nicolas; Ducournau, Corinne; Hutin, Stephanie; Mas, Philippe J.; Man, Petr; Forest, Éric; Hart, Darren J.; Peyrefitte, Christophe N.; Burmeister, W.P.; Iseni, Frédéric

doi:10.1038/s41467-017-01542-z

Cited by 40 publications

(90 citation statements)

References 67 publications

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“…Some of this research work explores the pathophysiology of the disease [49] , [50] , [51] and the potential ways for improving its prevention or treatment [52] , [53] . Research is also being conducted on poxvirus for improving or developing new vaccines against smallpox [54] , [55] , [56] and on viruses that cause haemorrhagic fever, particularly for the development of treatments [57] .…”

Section: Recent Achievements In Infectious Agents That Can Be Used Asmentioning

confidence: 99%

Contribution of the French army health service in support of expertise and research in infectiology in Africa

Pradines

Rogier²

2018

New Microbes and New Infections

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Historically, infectious diseases have caused more casualties than battle. The French military health service therefore developed a range of research on vector-borne diseases such as malaria and arboviruses, antibiotic resistance, infectious agents that can be used as biological weapons and vaccines. The main objective is to control naturally acquired or provoked infectious diseases and limit their impact on armed forces as well as on civilian populations in France or abroad, particularly in Africa and anywhere French armies may be deployed. The expertise of the military health service teams in manipulating agents requiring high level of biosafety precautions and in organizing and providing medical care in unnatural conditions, including the battlefield, associated with complementarity staff experience (physicians, biologists, epidemiologists, researchers, pharmacists, logisticians), has been used in the management of the Ebola outbreak in Guinea.

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Section: Recent Achievements In Infectious Agents That Can Be Used Asmentioning

confidence: 99%

Contribution of the French army health service in support of expertise and research in infectiology in Africa

Pradines

Rogier²

2018

New Microbes and New Infections

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“…More recently, we were successful in solving the crystal structure of the catalytic subunit of the VACV DNA polymerase ([ 71 ], Figure 4 B). The structure allowed us to delineate E9-specific inserts, and to position the enzyme in a global model of the DNA polymerase holoenzyme.…”

Section: Antiviralsmentioning

confidence: 99%

“…The structure allowed us to delineate E9-specific inserts, and to position the enzyme in a global model of the DNA polymerase holoenzyme. We showed that an insertion within the palm domain binds to A20, and represents a mode of processivity factor binding that differs from other members of family B polymerases [ 71 ]. As mentioned above, E9 is the target of CDV and its derivative CMX001, and also other inhibitors, such as aphidicolin, phosphonoacetic acid, and cytosine arabinoside.…”

Section: Antiviralsmentioning

confidence: 99%

“…The high-resolution structure of the polymerase active site will accelerate the development of new antiviral drugs. Furthermore, the identification of the E9/A20 interface will facilitate the design of new compounds or peptides that disrupt this interaction [ 71 ].…”

Section: Antiviralsmentioning

confidence: 99%

“…The various poxvirus-specific structural insertions are depicted in color. Some residues in insert 3 (dark green) were shown to be critical for E9/A20 interaction [ 71 ].…”

Section: Figurementioning

confidence: 99%

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The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus

Delaune¹,

Iseni²,

Ferrier-Rembert³

et al. 2017

Viruses

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Since the official declaration of smallpox eradication in 1980, the general population vaccination has ceased worldwide. Therefore, people under 40 year old are generally not vaccinated against smallpox and have no cross protection against orthopoxvirus infections. This naïve population may be exposed to natural or intentional orthopoxvirus emergences. The virology unit of the Institut de Recherche Biomédicale des Armées (France) has developed research programs on orthopoxviruses since 2000. Its missions were conceived to improve the diagnosis capabilities, to foster vaccine development, and to develop antivirals targeting specific viral proteins. The role of the virology unit was asserted in 2012 when the responsibility of the National Reference Center for the Orthopoxviruses was given to the unit. This article presents the evolution of the unit activity since 2000, and the past and current research focusing on orthopoxviruses.

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Evaluation of model refinement in CASP14

et al. 2021

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We report here an assessment of the model refinement category of the 14th round of Critical Assessment of Structure Prediction (CASP14). As before, predictors submitted up to five ranked refinements, along with associated residue-level error estimates, for targets that had a wide range of starting quality. The ability of groups to accurately rank their submissions and to predict coordinate error varied widely. Overall, only four groups out-performed a "naïve predictor" corresponding to the resubmission of the starting model. Among the top groups, there are interesting differences of approach and in the spread of improvements seen: some methods are more conservative, others more adventurous. Some targets were "double-barreled" for which predictors were offered a high-quality AlphaFold 2 (AF2)-derived prediction alongside another of lower quality. The AF2-derived models were largely unimprovable, many of their apparent errors being found to reside at domain and, especially, crystal lattice contacts. Refinement is shown to have a mixed impact overall on structure-based function annotation methods to predict nucleic acid binding, spot catalytic sites, and dock protein structures.

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The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding

Cited by 40 publications

References 67 publications

Contribution of the French army health service in support of expertise and research in infectiology in Africa

Contribution of the French army health service in support of expertise and research in infectiology in Africa

The French Armed Forces Virology Unit: A Chronological Record of Ongoing Research on Orthopoxvirus

Evaluation of model refinement in CASP14

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