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Review
. 2021 May;39(8):3025-3033.
doi: 10.1080/07391102.2020.1754293. Epub 2020 Apr 22.

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

Anwarul Hasan  1   2 , Bilal Ahamad Paray  3 , Arif Hussain  4 , Fikry Ali Qadir  5 , Farnoosh Attar  6 , Falah Mohammad Aziz  5 , Majid Sharifi  7 , Hossein Derakhshankhah  8 , Behnam Rasti  9 , Masoumeh Mehrabi  9 , Koorosh Shahpasand  10 , Ali Akbar Saboury  11 , Mojtaba Falahati  7
Affiliations
Review

A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

Anwarul Hasan et al. J Biomol Struct Dyn.2021 May.

Abstract

The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.

Keywords: Coronavirus; angiotensin-converting enzyme-2; enzyme inhibition; furin; spike protein.

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Figures

Figure 1.
Figure 1.
Schematic presentation of CoV (i), schematic of a protease cleavage site (ii), ribbon presentation of the structures of three HC proteases (iii), diagram of a CoV life cycle (iv). Abbreviation: transmembrane serine protease (TMPRSS). Reprinted with permission form Ref. (Millet & Whittaker, 2015).
Figure 2.
Figure 2.
(a) Schematic illustration of peptide cleavage induced by furin in different organisms (Braun & Sauter, 2019). (b) Schematic illustration of the residue sequence of SP from human SARS CoV [SP: signal peptide; FP: fusion peptide domain; HR-N: heptad repeat domain NH3+ terminal; HR-C: heptad repeat domain COO- terminal; TMD: transmembrane domain; CT: cytosolic tail (Basak et al., 2007). (c) CD signals of QSARS-4 peptide after incubation with different concentrations of recombinant furin (Basak et al., 2007). Reprinted with permission from Refs. (Basak et al., ; Braun & Sauter, 2019).
Figure 3.
Figure 3.
(a) Phylogenetic tree of some CoV from genera α-Cov and β-CoV, lineages a, b, c and d: SARS-CoV-2 (NC_045512.2), CoV-ZXC21 (MG772934), SARS-CoV (NC_004718.3), SARS-like BM4821 (MG772934), HCoV-OC43 (AY391777), HKU9-1 (EF065513), HCoV-NL63 (KF530114.1), HCoV229E (KF514433.1), MERS-CoV (NC019843.3), HKU1 (NC_006577.2) (i), code alignment and residue sequences of the S-protein from CoV-ZXC21 and SARS-CoV-2 (2019-nCoV) at the S1/S2 site (Coutard et al., 2020). (b) Comparison of the structures SARS-CoV RBD and its interaction with ACE-2 by the obtained molecular models of SARS-CoV-2 RBD (Chen et al., 2020). Reprinted with permission from Refs. (Chen et al., ; Coutard et al., 2020).
Figure 4.
Figure 4.
(a) APBS studies pointed out the mutation close to FCS may lead to the changes in the charge distribution of SP (Xi et al., 2020). The similarity between SARS-CoV and SARS-CoV-2 (Hoffmann et al., 2020). Reprinted with permission from Refs. (Hoffmann et al., ; Xi et al., 2020).
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References

    1. Ahmed S. F., Quadeer A. A., & McKay M. R. (2020). Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses, 12(3), 254 10.3390/v12030254 - DOI - PMC - PubMed
    1. Amer H., Alqahtani A. S., Alaklobi F., Altayeb J., & Memish Z. A. (2018). Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS-CoV): Revision of screening strategies urgently needed. International Journal of Infectious Diseases, 71, 113–116. 10.1016/j.ijid.2018.04.001 - DOI - PMC - PubMed
    1. Baron S. A., Devaux C., Colson P., Raoult D., & Rolain J.-M. (2020). Teicoplanin: An alternative drug for the treatment of coronavirus COVID-19? International Journal of Antimicrobial Agents, 5, 105944 10.1016/j.ijantimicag.2020.105944 - DOI - PMC - PubMed
    1. Basak A., Mitra A., Basak S., Pasko C., Chrétien M., & Seaton P. (2007). A fluorogenic peptide containing the processing site of human SARS corona virus S‐protein: Kinetic evaluation and NMR structure elucidation. ChemBioChem, 8(9), 1029–1037. 10.1002/cbic.200700007 - DOI - PMC - PubMed
    1. Belouzard S., Millet J. K., Licitra B. N., & Whittaker G. R. (2012). Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 4(6), 1011–1033. - PMC - PubMed

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