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Review
. 2020 Aug:175:93-98.
doi: 10.1016/j.biochi.2020.05.012. Epub 2020 May 29.

SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention

Ismail Sami Mahmoud  1 , Yazun Bashir Jarrar  2 , Walhan Alshaer  3 , Said Ismail  4
Affiliations
Review

SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention

Ismail Sami Mahmoud et al. Biochimie. 2020 Aug.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.

Keywords: ACE2; Drugs; Entry; Proteases; SARS-CoV-2.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
General structure of SARS coronavirus. (A) The structure of SARS-CoV-2 virion, with the main set of structural glycoproteins. (B) A linear map of domain organization of SARS-coronavirus spike (S) glycoprotein, the N-terminus S1 units contains the receptor binding domain (RBD) which is required for binding of the virus to ACE2. The C-terminus S2 harbours the functional elements required for fusion. It also contains a transmembrane domain (TM) for membrane anchoring and a cytoplasmic tail for appropriate intracellular trafficking.
Fig. 2
Fig. 2
Routes of SARS-CoV-2 virus entry into target cells. Binding of a viral (S) glycoprotein to ACE2 receptor can be followed by receptor mediated endocytosis, which ends up in endosomal compartment, where an increase in H+ influx into the endosome activates cathepsin L which activates viral (S) glycoprotein and facilitates viral membrane fusion and releases of ssRNA out of the endosome (left). Chloroquine and hydroxychloroquine are known to block virus infection mainly by increasing endosomal pH required for virus/cell fusion. The thiocarbazate SID26681509 and teicoplanin are inhibitors of cathepsin L. Alternatively, proteolytic cleavage of the viral (S) protein by TMPRSS2 protease on the surface of host cell can induce direct fusion of the viral and plasma membrane leading to release of the viral ssRNA into the cytoplasm (right). The camostat mesylate drug inhibits TMPRSS2 activity.
Fig. 3
Fig. 3
Chemical structure of candidate drugs of SARS-CoV-2 infection.
See this image and copyright information in PMC

References

    1. Jiang S., Shi Z., Shu Y. A distinct name is needed for the new coronavirus. Lancet. 2020;395(10228):949. doi: 10.1016/S0140-6736(20)30419-0. - DOI - PMC - PubMed
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention [published online ahead of print, 2020 feb 24] J. Am. Med. Assoc. 2020 doi: 10.1001/jama.2020.2648. 10.1001/jama.2020.2648. - DOI - PubMed
    1. Patel A.B., Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence? [published online ahead of print, 2020 mar 24] J. Am. Med. Assoc. 2020 doi: 10.1001/jama.2020.4812. 10.1001/jama.2020.4812. - DOI - PubMed
    1. Zhou P., Yang X.L., Wang X.G. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi: 10.1038/s41586-020-2012-7. - DOI - PMC - PubMed
    1. Drosten C., Günther S., Preiser W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348(20):1967–1976. doi: 10.1056/NEJMoa030747. - DOI - PubMed

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