Sars-Cov-2 And Betacoronavirus: What Have We Learned In 8 Months?

Kwiatek, Agnieszka; Adamczyk-Popławska, Monika

doi:10.21307/PM-2020.59.3.14

Figures & Tables

Scheme illustrating the spike protein of SARS-CoV-2
(A) Scheme of the three-dimensional structure. S1 – S1 subunit, S2 – S2 subunit, RBD – receptor binding domain, TM – transmembrane domain, IC – intracellular tail. The arrows indicate the cleavage site between S1 and S2 subunits; (B) Organization of SARS-CoV-2 spike protein. SP- signal peptide, NTD – N-terminal domain, RBD – receptor binding domain, FP – fusion peptide, IFP – internal fusion peptide, HR1/HR2 – heptad repeat 1/2, TM – transmembrane domain. Arrows indicate the cleavage site S1/S2 and S’; (C) Sequence comparison of the spike proteins of SARS-CoV-2, SARS-CoV and MERS-CoV in a region at S1/S2 boundary. Thin arrows indicate the cleavage site S1/S2 and S’, and wide – the furin cleavage site. The cleavage sites are surrounded by frames. Additionally, site cleaved by furin is grey highlighted. Below the amino acids positions are given. — Scheme illustrating the spike protein of SARS-CoV-2 (A) Scheme of the three-dimensional structure. S1 – S1 subunit, S2 – S2 subunit, RBD – receptor binding domain, TM – transmembrane domain, IC – intracellular tail. The arrows indicate the cleavage site between S1 and S2 subunits; (B) Organization of SARS-CoV-2 spike protein. SP- signal peptide, NTD – N-terminal domain, RBD – receptor binding domain, FP – fusion peptide, IFP – internal fusion peptide, HR1/HR2 – heptad repeat 1/2, TM – transmembrane domain. Arrows indicate the cleavage site S1/S2 and S’; (C) Sequence comparison of the spike proteins of SARS-CoV-2, SARS-CoV and MERS-CoV in a region at S1/S2 boundary. Thin arrows indicate the cleavage site S1/S2 and S’, and wide – the furin cleavage site. The cleavage sites are surrounded by frames. Additionally, site cleaved by furin is grey highlighted. Below the amino acids positions are given.

Functions of Betacoronavirus non-structural proteins

Protein	Function
nsp1	Inhibits host translation and gene expression by mRNA degradation and binding 40S ribosome subunit resulting in blocking innate immune response [29, 30, 64].
nsp2	Binds to prohibitin proteins, function not determined [11, 22]
nsp3	PL2pro multi-domain transmembrane protein, possessing:
	• ADRP activity, promotes cytokine expression;
	• PLPro/Deubiquitinase domain, cleaves viral polyprotein;
	• antagonist of IRF3 and NF-τB Signaling resulting in blocking host immune response;
	• Ubl1 and Ac domains, interact with N protein;
	• Ubl2, NAB, G2M, SUD, Y domains, unknown functions [9, 16, 19, 44, 54].
nsp4	Interacts with nsp3; induce the Formation of Double-Membrane Vesicles [2, 48].
nsp5	MoPro or 3CLpro processing of viral polyproteins [66].
nsp6	Potential transmembrane scaffold protein [40].
nsp7	Forms hexadecameric nsp7-nsp8 complex, essential co-factor of nsp12, may act as processivity clamp for RNA polymerase [34, 77].
nsp8	Forms hexadecameric nsp7-nsp8 complex, essential co-factor of nsp12, may act as primase [34, 77].
nsp9	Single-stranded RNA binding protein [17].
nsp10	Cofactor for nsp16 and nsp14, forms heterodimer with both and stimulates ExoN and S-adenosylmethionine-dependent (nucleoside-2′-O)-methyltransferase [6, 10, 13, 41].
nsp12	RNA-dependent RNA polymerase (RdRp) [34].
nsp13	Superfamily 1-like helicase (HEL1), RNA helicase, 5’ triphosphatase [28].
nsp14	• C-terminal domain functions as a (guanine-N7) methyl transferase (N7-MTase) for mRNA capping.
nsp14	• N-terminal exoribonuclease (ExoN) domain displays a 3′-5′ exoribonuclease proofreading activity [6, 41].
nsp15	NendoU, uridylate-specific endoribonuclease [78].
nsp16	S-adenosylmethionine-dependent (nucleoside-2′-O)-methyltransferase modifying the RNA cap at ribose 2′-O positions [6, 10].

Sars-Cov-2 And Betacoronavirus: What Have We Learned In 8 Months?

Figures & Tables

Fig. 1.

Functions of Betacoronavirus non-structural proteins

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