The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.
The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2
Open accessAbstract
The bifunctional nsp14 subunit of the coronavirus replicase contains 3′-to-5′ exoribonuclease (ExoN) and guanine-N7-methyltransferase domains. For the betacoronaviruses MHV and SARS-CoV, ExoN was reported to promote the fidelity of genome replication, presumably by mediating a form of proofreading. For these viruses, ExoN knockout mutants are viable while displaying an increased mutation frequency. Strikingly, we have now established that the equivalent ExoN knockout mutants of two other betacoronaviruses, MERS-CoV and SARS-CoV-2, are nonviable, suggesting an additional and critical ExoN function in their replication. This is remarkable in light of the very limited genetic distance between SARS-CoV and SARS-CoV-2, which is highlighted, for example, by 95% amino acid sequence identity in their nsp14 sequences. For (recombinant) MERS-CoV nsp14, both its enzymatic activities were evaluated using newly developed in vitro assays that can be used to characterize these key replicative enzymes in more detail and explore their potential as target for antiviral drug development.
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Cited by
Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting
Robson, F., Khan, K. S., Le, T. K., Paris, C., Demirbag, S., Barfuss, P., Rocchi, P., & Ng, W.-L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.07.027 · Cited by 396
Tasakis, R. N., Samaras, G., Jamison, A., Lee, M., Paulus, A., Whitehouse, G., Verkoczy, L., Papavasiliou, F. N., & Diaz, M. (2021) · PLOS ONE · doi:10.1371/journal.pone.0255169 · Cited by 26
Yoshida, A., Okamura, S., Torii, S., Komatsu, S., Miyazato, P., Sasaki, H., Ueno, S., Suzuki, H., Kamitani, W., Ono, C., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105412 · Cited by 20
Metadata
- Authors
- Ogando, N. S., Zevenhoven-Dobbe, J. C., van der Meer, Y., Bredenbeek, P. J., Posthuma, C. C., & Snijder, E. J.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2020-11-09
- Volume
- 94
- Issue
- 23
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W3086108939
- Cited by
- 282
- References
- 99
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ogando, N. S., Zevenhoven-Dobbe, J. C., van der Meer, Y., Bredenbeek, P. J., Posthuma, C. C., & Snijder, E. J. (2020). The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2. Journal of Virology. https://doi.org/10.1128/jvi.01246-20
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