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Covid-19: what treatments are being investigated?

BMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m1252 (Published 26 March 2020) Cite this as: BMJ 2020;368:m1252

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ENDOPLASMIC RETICULUM-GOLGI INTERMEDIATE COMPARTMENT: A NOVEL TARGET FOR SARS-COV-2 THERAPIES?

Dear Editor,

several ongoing therapeutic and prophylactic efforts against SARS-Cov-2 focus on the viral structural proteins. Indeed, coronavirus virus particles are equipped with four main structural proteins: the spike, membrane, envelope, and nucleocapsid proteins (Fehr and Perlman, 2016; Chen et al., 2020). Nevertheless, another underrated virionic component, this time entirely provided by the host, could stand for a feasible therapeutic target: the lipid wall derived from the human endoplasmic reticulum-Golgi intermediate compartment (ERGIC), i.e., the vesicular-tubular cluster which mediates trafficking between endoplasmic reticulum (ER) and Golgi complex (Appenzeller-Herzog and Hauri, 2006).

Like other enveloped viruses that assemble intracellularly, coronaviruses use the ERGIC membranes as a physical support for different steps of their vital cycle, such as replication and assembly by budding (Risco et al. 2002). Following replication and subgenomic RNA synthesis, viral structural proteins are translated and inserted into ER (Krijnse-Locker et al., 1994). These proteins move along the secretory pathway into ERGIC. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis. Therefore, coronaviruses membrane displays markers for the endoplasmic reticulum and Golgi (Brian and Baric, 2005) that are more preserved, less variable and therapeutically less difficult to tackle than the ever-changing and highly mutating structural proteins.

It is noteworthy that antibodies against ER and ERGIC are already available, and some of them have been also reported from several diseases (Hong et al., 2004). We suggest to use such antibodies against human host-derived components of the SARS-Cov-2 membrane to stop the viral progression at the beginning of upper respiratory airways invasion, when the symptoms of COVID-19 are still moderate (cough, light dyspnea, etc). These antibodies could be sprayed in the upper and lower airways of swab-positive COVID-19 patients with mild/moderate symptoms: this would lead to impairment of virion membrane, before the SARS-Cov-2 would be able to proceed towards the lung epithelium, where it frequently causes lethal interstitial pneumonia in elderly and/or impaired subjects.

REFERENCES

1) Appenzeller-Herzog C, Hauri H-P. 2006. The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function. Journal of Cell Science 2006 119: 2173-2183; doi: 10.1242/jcs.03019.
2) Brian D.A., Baric R.S. 2005. Coronavirus Genome Structure and Replication. In: Enjuanes L. (eds) Coronavirus Replication and Reverse Genetics. Current Topics in Microbiology and Immunology, vol 287. Springer, Berlin, Heidelberg.
3) Chen Y, Liu Q1, Guo D. 2020. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol. 2020 Apr;92(4):418-423. doi: 10.1002/jmv.25681.
4) Fehr AR, Perlman S. 2016. Coronaviruses: An Overview of Their Replication and Pathogenesis. Methods Mol Biol. 2015; 1282: 1–23. doi: 10.1007/978-1-4939-2438-7_1.
5) Hong HS, Chung WH, Hung SI, Chen MJ, Lee SH, Yang LC. 2004. Clinical association of anti-golgi autoantibodies and their autoantigens. Scand J Immunol. 2004 Jan;59(1):79-87.
6) Krijnse-Locker J, Ericsson M, Rottier PJ, Griffiths G. Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step. J Cell Biol. 1994 Jan;124(1-2):55-70.
7) Risco C, Rodríguez JR, López-Iglesias C, Carrascosa JL, Esteban M, Rodríguez D. 2002. Endoplasmic reticulum-Golgi intermediate compartment membranes and vimentin filaments participate in vaccinia virus assembly. J Virol. 2002 Feb;76(4):1839-55.

Arturo Tozzi
Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA
tozziarturo@libero.it
Arturo.Tozzi@unt.edu

Competing interests: No competing interests

28 March 2020
Arturo Tozzi
Pediatrician
University of North Texas, Denton, Texas, USA
1155 Union Circle, #311427Denton, TX 76203-5017 USA