Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response (PubMed:23035226). May disrupt nuclear pore function by binding and displacing host NUP93 (PubMed:30943371). May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2 (PubMed:19640993). Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses (PubMed:19640993). Responsible for the cleavages located at the N-terminus of the replicase polyprotein (PubMed:16306590). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (PubMed:16306590, PubMed:17692280). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24410069). Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3 (PubMed:19369340, PubMed:24622840). Prevents also host NF-kappa-B signaling (PubMed:19369340, PubMed:24622840). Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:23943763). Alone appears incapable to induce membrane curvature, but together with nsp3 is able to induce paired membranes. Nsp3, nsp4 and nsp6 together are sufficient to form DMV. Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP). May cleave host ATP6V1G1 thereby modifying host vacuoles intracellular pH. Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (PubMed:24991833, PubMed:24410069). Nsp3, nsp4 and nsp6 together are sufficient to form DMV (PubMed:24991833, PubMed:24410069). Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes (PubMed:24991833). Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. Plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA. Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation. Responsible for replication and transcription of the viral RNA genome. Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium. Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity (PubMed:16549795, PubMed:20421945, PubMed:22635272). Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens (PubMed:23966862, PubMed:29511076, PubMed:21593585). Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (PubMed:28158275, PubMed:18045871). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (PubMed:16828802). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (PubMed:28158275, PubMed:18045871). Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs (PubMed:18417574, PubMed:22022266,PubMed:20421945). N7-methyl guanosine cap is a prerequisite for binding of nsp16 (PubMed:18417574). Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system (PubMed:18417574, PubMed:22022266,PubMed:20421945). a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1) ATP + H2O = ADP + H(+) + phosphate ATP + H2O = ADP + H(+) + phosphate TSAVLQ-|-SGFRK-NH2 and SGVTFQ-|-GKFKK the two peptides corresponding to the two self-cleavage sites of the SARS 3C-like proteinase are the two most reactive peptide substrates. The enzyme exhibits a strong preference for substrates containing Gln at P1 position and Leu at P2 position. Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-adenosyl-L-homocysteine uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA Likely affects Nsp15 binding to RNA. Inhibited by Remdesivir (GS-5734). The kinetic parameters are studied for the 3C-like proteinase domain. Optimum pH is 7.0 for 3C-like proteinase activity. Interacts with host PHB and PHB2. Interacts with papain-like protease nsp3 and non-structural protein 6. Monomer. Homodimer. Only the homodimer shows catalytic activity. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure. Eight copies of nsp7 and eight copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling ring structure (PubMed:16228002). Interacts with ORF6 protein (PubMed:17532020). Homodimer. Homododecamer (PubMed:16873247). Interacts with proofreading exoribonuclease nsp14 and 2'-O-methyltransferase nsp16; these interactions enhance nsp14 and nsp16 enzymatic activities (PubMed:18827877, PubMed:22022266, PubMed:22635272). Interacts (via N-terminus) with host DDX1 (PubMed:20573827). Interacts with non-structural protein 10 (PubMed:18827877). Homohexamer. Interacts with nsp10. Localizes in virally-induced cytoplasmic double-membrane vesicles. nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. The helicase interacts with the N protein in membranous complexes and colocalizes with sites of synthesis of new viral RNA. Isoform replicase polyprotein 1ab is produced by -1 ribosomal frameshifting at the 1a-1b genes boundary. Isoform replicase polyprotein 1a is produced by conventional translation. The hydrophobic region HD1 probably mediates the membrane association of the replication complex. The hydrophobic region HD2 probably mediates the membrane association of the replication complex. The hydrophobic region HD3 probably mediates the membrane association of the replication complex. Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (PubMed:32083638, PubMed:16306590, PubMed:12917450, PubMed:15331731, PubMed:15564471). 3C-like proteinase nsp5 liberates nsps 6-16 from the polyprotein (PubMed:32083638). Papain-like and 3C-like proteinases are autocatalytically processed. Belongs to the coronaviruses polyprotein 1ab family. Isolates SZ3 and SZ16 have been isolated from Paguma larvata and are described as SARS-like in literature.