SARS-CoV-2 Virion Stabilization by Zn Binding

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2020 Nov 16

PMID 33195401

Citations 10

Authors

Silvia Morante

Giovanni La Penna

Giancarlo Rossi

Francesco Stellato

Affiliations

Soon will be listed here.

Abstract

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation.

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References

Gammoh N, Rink L . Zinc in Infection and Inflammation. Nutrients. 2017; 9(6). PMC: 5490603. DOI: 10.3390/nu9060624. View

Tochio N, Umehara T, Nakabayashi K, Yoneyama M, Tsuda K, Shirouzu M . Solution structures of the DNA-binding domains of immune-related zinc-finger protein ZFAT. J Struct Funct Genomics. 2015; 16(2):55-65. PMC: 4427657. DOI: 10.1007/s10969-015-9196-3. View

Maier J, Martinez C, Kasavajhala K, Wickstrom L, Hauser K, Simmerling C . ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB. J Chem Theory Comput. 2015; 11(8):3696-713. PMC: 4821407. DOI: 10.1021/acs.jctc.5b00255. View

Xu J, Zhao S, Teng T, Abdalla A, Zhu W, Xie L . Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020; 12(2). PMC: 7077191. DOI: 10.3390/v12020244. View

Swiecki M, Omattage N, Brett T . BST-2/tetherin: structural biology, viral antagonism, and immunobiology of a potent host antiviral factor. Mol Immunol. 2013; 54(2):132-9. DOI: 10.1016/j.molimm.2012.11.008. View

Kluska K, Peris-Diaz M, Plonka D, Moysa A, Dadlez M, Deniaud A . Formation of highly stable multinuclear AgS clusters in zinc fingers disrupts their structure and function. Chem Commun (Camb). 2020; 56(9):1329-1332. DOI: 10.1039/c9cc09418k. View

Gati C, Stetsenko A, Slotboom D, Scheres S, Guskov A . The structural basis of proton driven zinc transport by ZntB. Nat Commun. 2017; 8(1):1313. PMC: 5670123. DOI: 10.1038/s41467-017-01483-7. View

Le Tortorec A, Willey S, Neil S . Antiviral inhibition of enveloped virus release by tetherin/BST-2: action and counteraction. Viruses. 2011; 3(5):520-40. PMC: 3185764. DOI: 10.3390/v3050520. View

La Penna G, Morante S, Perico A, Rossi G . Designing generalized statistical ensembles for numerical simulations of biopolymers. J Chem Phys. 2004; 121(21):10725-41. DOI: 10.1063/1.1795694. View

10.

Gordon D, Jang G, Bouhaddou M, Xu J, Obernier K, White K . A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020; 583(7816):459-468. PMC: 7431030. DOI: 10.1038/s41586-020-2286-9. View

11.

Chaturvedi U, Shrivastava R . Interaction of viral proteins with metal ions: role in maintaining the structure and functions of viruses. FEMS Immunol Med Microbiol. 2005; 43(2):105-14. PMC: 7110337. DOI: 10.1016/j.femsim.2004.11.004. View

12.

Taylor J, Coleman C, Postel S, Sisk J, Bernbaum J, Venkataraman T . Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. J Virol. 2015; 89(23):11820-33. PMC: 4645327. DOI: 10.1128/JVI.02274-15. View

13.

Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y . Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020; 10(5):766-788. PMC: 7102550. DOI: 10.1016/j.apsb.2020.02.008. View

14.

Raffa D, Rickard G, Rauk A . Ab initio modelling of the structure and redox behaviour of copper(I) bound to a His-His model peptide: relevance to the beta-amyloid peptide of Alzheimer's disease. J Biol Inorg Chem. 2006; 12(2):147-64. DOI: 10.1007/s00775-006-0175-9. View

15.

Pang Y . Successful molecular dynamics simulation of two zinc complexes bridged by a hydroxide in phosphotriesterase using the cationic dummy atom method. Proteins. 2001; 45(3):183-9. DOI: 10.1002/prot.1138. View

16.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View

17.

Chasapis C . Interactions between metal binding viral proteins and human targets as revealed by network-based bioinformatics. J Inorg Biochem. 2018; 186:157-161. DOI: 10.1016/j.jinorgbio.2018.06.012. View

18.

Zhang J, Yang W, Piquemal J, Ren P . Modeling Structural Coordination and Ligand Binding in Zinc Proteins with a Polarizable Potential. J Chem Theory Comput. 2012; 8(4):1314-1324. PMC: 3383645. DOI: 10.1021/ct200812y. View

19.

Te Velthuis A, van den Worm S, Sims A, Baric R, Snijder E, van Hemert M . Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010; 6(11):e1001176. PMC: 2973827. DOI: 10.1371/journal.ppat.1001176. View

20.

Kirchdoerfer R, Ward A . Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun. 2019; 10(1):2342. PMC: 6538669. DOI: 10.1038/s41467-019-10280-3. View