D
IPR009461

Non-structural protein NSP16, coronavirus-like

InterPro entry
Short nameNSP16_CoV-like
Overlapping
homologous
superfamilies
 
domain relationships

Description

This domain covers the NSP16 region of the coronavirus polyprotein. It was originally named NSP13 and later changed to NSP16 to distinguish it from the helicase region
[1]
. NSP16 is a 7-methylguanine-triphosphate-adenosine (m7GpppA)-specific, SAM-dependent 2'-O-MTase that has selective RNA binding properties and is a cap-0 binding protein. It contains a highly conserved catalytic tetrad (K-D-K-E) that is a hallmark of RNA 2'O-MTases
[4, 2, 3]
. NSP16 plays a key role in viral replication as it is involved in immune response evasion through the 2'-O-methylation of coronavirus RNA, which is essential for preventing recognition by the host. It mimics the human protein CMTr1 and, unlike CMTr1, it requires NSP10 as a binding partner to activate its enzymatic activity
[2]
. Structural analysis in NSP16 from SARS-CoV-2 identified a cryptic pocket (also present in other coronavirus such as SARS-CoV-1 and MERS) not present in human CMTr1, and the fact that NSP16 is one of the most conserved proteins of SARS-CoV-2 and related viruses, make it an interesting target for developing new antiviral treatment for COVID-19 and other diseases caused by coronaviruses
[3]
.

References

1.mRNA cap-1 methyltransferase in the SARS genome. von Grotthuss M, Wyrwicz LS, Rychlewski L. Cell 113, 701-2, (2003). View articlePMID: 12809601

2.SARS-CoV-2 Nsp16 activation mechanism and a cryptic pocket with pan-coronavirus antiviral potential. Vithani N, Ward MD, Zimmerman MI, Novak B, Borowsky JH, Singh S, Bowman GR. Biophys J 120, 2880-2889, (2021). PMID: 33794150

3.High-resolution structures of the SARS-CoV-2 2'-<i>O</i>-methyltransferase reveal strategies for structure-based inhibitor design. Rosas-Lemus M, Minasov G, Shuvalova L, Inniss NL, Kiryukhina O, Brunzelle J, Satchell KJF. Sci Signal 13, (2020). PMID: 32994211

4.Coronavirus nonstructural protein 16 is a cap-0 binding enzyme possessing (nucleoside-2'O)-methyltransferase activity. Decroly E, Imbert I, Coutard B, Bouvet M, Selisko B, Alvarez K, Gorbalenya AE, Snijder EJ, Canard B. J. Virol. 82, 8071-84, (2008). PMID: 18417574

Cross References

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