nsp10:nsp14 binds to ExoN inhibitors

Stable Identifier
R-HSA-9731708
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol
ReviewStatus
5/5
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nsp10:nsp14 binds to ExoN inhibitors
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Nsp14:nsp10 (ExoN) is a highly versatile nuclease capable of digesting a wide variety of RNA structures, including those with a blocked 3’-terminus. The enzyme needs Mg2+ or Mn2+ as cofactor (Saramago et al, 2021). Raltegravir and ebselen have been shown to inhibit the nsp14:nsp10 complex in vitro (Baddock et al, 2020). Raltegravir is an approved HIV-1 integrase strand transfer inhibitor (Hicks & Gulick, 2009). Ebselen is a mimic of glutathione peroxidase with antioxidant activity, as well as an inhibitor of SARS-CoV-2 PLpro protease (nsp3) and main protease (nsp5) (Jin et al, 2020; Weglarz-Tomczak et al, 2021).
Literature References
PubMed ID Title Journal Year
32272481 Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors

Duan, Y, Zhang, L, Jin, Z, Jiang, R, Shi, Z, Deng, Y, Qin, C, Zhang, B, Yang, H, Wang, L, Xu, Y, Liu, H, You, T, Du, X, Peng, C, Liu, M, Liu, X, Xu, W, Yang, X, Yang, X, Liu, F, Li, X, Rao, Z, Xiao, G, Zhao, Y, Jiang, H, Liu, X, Bai, F, Yu, J, Yang, K, Guddat, LW

Nature 2020
19231980 Raltegravir: the first HIV type 1 integrase inhibitor

Hicks, C, Gulick, RM

Clin Infect Dis 2009
33705595 New targets for drug design: importance of nsp14/nsp10 complex formation for the 3'-5' exoribonucleolytic activity on SARS-CoV-2

Saramago, M, Arraiano, CM, Matos, RG, Viegas, SC, Souza, CS, Costa, VG, Bárria, C, Lousa, D, Domingues, S, Soares, CM

FEBS J 2021
33574416 Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2

Tomczak, JM, Brul, S, Talma, M, Weglarz-Tomczak, E, Giurg, M, Burda-Grabowska, M

Sci Rep 2021
  Characterisation of the SARS-CoV-2 ExoN (nsp14ExoN-nsp10) complex: implications for its role in viral genome stability and inhibitor identification

McHugh, PJ, Cruz-Migoni, A, Gileadi, O, Brolih, S, Baddock, HT, Ratnaweera, M, Swift, LP, Yosaatmadja, Y, Schofield, CJ, Bielinski, M

   
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Stephan, R  (2021-05-21)
Created
Stephan, R  (2021-05-24)
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