Nsp1 |
|
Cyclophilin (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) |
(Pfefferle et al., 2011Pfefferle S, Schöpf J, Kögl M, Friedel CC, Müller MA, Carbajo-Lozoya J, Stellberger T, von Dall’Armi E, Herzog P, Kallies S et al. (2011) The SARS-coronavirus-host interactome: Identification of cyclophilins as target for pan-coronavirus inhibitors. PLoS Pathog 7:e1002331.) |
Nsp2 |
|
Prohibitin |
(Cornillez-Ty et al., 2009Cornillez-Ty CT, Liao L, Yates JR, Kuhn P and Buchmeier MJ (2009) Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling. J Virol 83:10314-10318.) |
Nsp3 |
N protein |
TGF-β1 (indirect); STING-TRAF3-TBK1; RCHY1, p53 and IRF3 |
(Hurst et al., 2013Hurst KR, Koetzner CA and Masters PS (2013) Characterization of a critical interaction between the coronavirus nucleocapsid protein and nonstructural protein 3 of the viral replicase-transcriptase complex. J Virol 87:9159-9172.; Chen et al., 2014Chen X, Yang X, Zheng Y, Yang Y, Xing Y and Chen Z (2014) SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell 5:369-381.; Ma-Lauer et al., 2016Ma-Lauer Y, Carbajo-Lozoya J, Hein MY, Müller MA, Deng W, Lei J, Meyer B, Kusov Y, Von Brunn B, Bairad DR et al. (2016) p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PL pro via E3 ubiquitin ligase RCHY1. Proc Natl Acad Sci U S A 113:E5192-E5201.; Li et al., 2016Li S-W, Wang C-Y, Jou Y-J, Yang T-C, Huang S-H, Wan L, Lin Y-J and Lin C-W (2016) SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway. Sci Rep 6:25754.) |
Nsp5 |
|
STAT2 |
(Zhu et al., 2017Zhu X, Wang D, Zhou J, Pan T, Chen J, Yang Y, Lv M, Ye X, Peng G, Fang L et al. (2017) Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving STAT2. J Virol 91:e00003-17) |
Nsp6 |
|
Autophagosome |
(Cottam et al., 2014Cottam EM, Whelband MC and Wileman T (2014) Coronavirus NSP6 restricts autophagosome expansion. Autophagy 10:1426-1441.) |
Nsp7 |
Nsp8 |
|
(te Velthuis et al., 2012te Velthuis AJW, van den Worm SHE and Snijder EJ (2012) The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res 40:1737-1747.) |
Nsp8 |
Nsp7 |
|
(te Velthuis et al., 2012te Velthuis AJW, van den Worm SHE and Snijder EJ (2012) The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. Nucleic Acids Res 40:1737-1747.) |
Nsp9 |
|
TRIM59 and MIB1 |
(Gordon et al., 2020Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459-468.) |
Nsp10 |
Nsp14 and Nsp16 |
|
(Decroly et al., 2011Decroly E, Debarnot C, Ferron F, Bouvet M, Coutard B, Imbert I, Gluais L, Papageorgiou N, Sharff A, Bricogne G et al. (2011) Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2’-O-methyltransferase nsp10/nsp16 complex. PLoS Pathog 7:e1002059.) |
Nsp13 |
|
TBK1, TBKBP1, TLE1, 3, and 5 |
(Gordon et al., 2020Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459-468.) |
Nsp15 |
|
Apoptosis and dsRNA cell sensors; Rb |
(Bhardwaj et al., 2012Bhardwaj K, Liu P, Leibowitz JL and Kao CC (2012) The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein. J Virol 86:4294-4304.; Deng et al., 2017Deng X, Hackbart M, Mettelman RC, O’Brien A, Mielech AM, Yi G, Kao CC and Baker SC (2017) Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages. Proc Natl Acad Sci U S A 114:E4251-E4260.) |
Nsp16 |
|
RIG-I and MDA5 (innate immunity) |
(Shi et al., 2019Shi P, Su Y, Li R, Liang Z, Dong S and Huang J (2019) PEDV nsp16 negatively regulates innate immunity to promote viral proliferation. Virus Res 265:57-66.) |
RTC |
|
Translation initiation factors (eIF3E, eIF3F and eIF3I); Intracellular transport (SNARE proteins; SRP54a and SRP68 proteins); autophagy-related factors and ubiquitin-dependent ERAD components |
(V’kovski et al., 2019V’kovski P, Gerber M, Kelly J, Pfaender S, Ebert N, Braga Lagache S, Simillion C, Portmann J, Stalder H, Gaschen V et al. (2019) Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling. Elife 8:1-30.) |
S |
M |
ACE2; TMPRSS2; apoptosis |
(Yeung et al., 2008Yeung Y-S, Yip C-W, Hon C-C, Chow KYC, Ma ICM, Zeng F and Leung FCC (2008) Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: Insights on viral regulation of apoptosis and proliferation. Virology 371:32-43.; Neuman et al., 2011Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG et al. (2011) A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 174:11-22.; Yan et al., 2020Yan R, Zhang Y, Li Y, Xia L, Guo Y and Zhou Q (2020) Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 367:1444-1448.) |
E |
M protein |
PALS1 (tight junction); BRD2 and BRD4; palmitoylations |
(Boscarino et al., 2008Boscarino JA, Logan HL, Lacny JJ and Gallagher TM (2008) Envelope protein palmitoylations are crucial for murine coronavirus assembly. J Virol 82:2989-2999.; Chen et al., 2009Chen Y, Cai H, Pan J, Xiang N, Tien P, Ahola T and Guo D (2009) Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. Proc Natl Acad Sci U S A 106:3484-3489.; Teoh et al., 2010Teoh K-T, Siu Y-L, Chan W-L, Schlüter MA, Liu C-J, Peiris JSM, Bruzzone R, Margolis B and Nal B (2010) The SARS coronavirus E protein interacts with PALS1 and alters tight junction formation and epithelial morphogenesis. Mol Biol Cell 21:3838-3852.; Gordon et al., 2020Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459-468.) |
M |
E protein; N protein; S protein |
|
(Chen et al., 2009Chen Y, Cai H, Pan J, Xiang N, Tien P, Ahola T and Guo D (2009) Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase. Proc Natl Acad Sci U S A 106:3484-3489.; Hurst et al., 2009Hurst KR, Koetzner CA and Masters PS (2009) Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. J Virol 83:7221-7234. ; Neuman et al., 2011Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG et al. (2011) A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 174:11-22.) |
N |
M protein; Nsp3 |
RNA interference machinery; NCL; NPM; NONO; PABP; HNRNPs; ribosomal proteins; caprin-1; G3BPs; GSK3; PACT; TRIM25; cyclin D; LARP1; CK2; UPF1; MOV10 |
(Chen et al., 2002Chen H, Wurm T, Britton P, Brooks G and Hiscox JA (2002) Interaction of the coronavirus nucleoprotein with nucleolar antigens and the host cell. J Virol 76:5233-5250.; Surjit et al., 2006Surjit M, Liu B, Chow VTK and Lal SK (2006) The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells. J Biol Chem 281:10669-10681.; Hurst et al., 2009Hurst KR, Koetzner CA and Masters PS (2009) Identification of in vivo-interacting domains of the murine coronavirus nucleocapsid protein. J Virol 83:7221-7234. ; Emmott et al., 2013Emmott E, Munday D, Bickerton E, Britton P, Rodgers MA, Whitehouse A, Zhou E-M and Hiscox JA (2013) The cellular interactome of the coronavirus infectious bronchitis virus nucleocapsid protein and functional implications for virus biology. J Virol 87:9486-9500.; Hurst et al., 2013Hurst KR, Koetzner CA and Masters PS (2013) Characterization of a critical interaction between the coronavirus nucleocapsid protein and nonstructural protein 3 of the viral replicase-transcriptase complex. J Virol 87:9159-9172.; Cui et al., 2015Cui L, Wang H, Ji Y, Yang J, Xu S, Huang X, Wang Z, Qin L, Tien P, Zhou X et al. (2015) The nucleocapsid protein of coronaviruses acts as a viral suppressor of rna silencing in mammalian cells. J Virol 89:9029-9043.; Ding et al., 2017Ding Z, Fang L, Yuan S, Zhao L, Wang X, Long S, Wang M, Wang D, Foda MF and Xiao S (2017) The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: Attenuation of PACT-mediated RIG-I/MDA5 activation. Oncotarget 8:49655-49670.; Gordon et al., 2020Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459-468.) |
ORF3a |
|
TRAF3 and ASC; caveolin-1; eIF2α and PERK |
(Padhan et al., 2007Padhan K, Tanwar C, Hussain A, Hui PY, Lee MY, Cheung CY, Peiris JSM and Jameel S (2007) Severe acute respiratory syndrome coronavirus Orf3a protein interacts with caveolin. J Gen Virol 88:3067-3077.; Minakshi et al., 2009Minakshi R, Padhan K, Rani M, Khan N, Ahmad F and Jameel S (2009) The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS One 4:e8342.; Siu et al., 2019Siu K, Yuen K, Castano‐Rodriguez C, Ye Z, Yeung M, Fung S, Yuan S, Chan C, Yuen K, Enjuanes L et al. (2019) Severe acute respiratory syndrome Coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3‐dependent ubiquitination of ASC. FASEB J 33:8865-8877.) |
ORF6 |
Nsp8 |
karyopherin alpha 2 and karyopherin beta 1; NUP98-RAE1 |
(Kumar et al., 2007Kumar P, Gunalan V, Liu B, Chow VTK, Druce J, Birch C, Catton M, Fielding BC, Tan Y-J and Lal SK (2007) The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its ORF6 accessory protein. Virology 366:293-303.; Frieman et al., 2007Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P and Baric RS (2007) Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol 81:9812-9824.; Gordon et al., 2020Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459-468.) |
ORF7a |
ORF3 |
Type I IFN response; BST-2; cyclin D3/pRb pathway |
(Yuan et al., 2006Yuan X, Wu J, Shan Y, Yao Z, Dong B, Chen B, Zhao Z, Wang S, Chen J and Cong Y (2006) SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway. Virology 346:74-85.; Dedeurwaerder et al., 2014Dedeurwaerder A, Olyslaegers DAJ, Desmarets LMB, Roukaerts IDM, Theuns S and Nauwynck HJ (2014) ORF7-encoded accessory protein 7a of feline infectious peritonitis virus as a counteragent against IFN-α-induced antiviral response. J Gen Virol 95:393-402. ; Taylor et al., 2015Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum JG, Venkataraman T, Sundberg EJ and Frieman MB (2015) Severe acute respiratory syndrome coronavirus ORF7a inhibits bone marrow stromal antigen 2 virion tethering through a novel mechanism of glycosylation interference. J Virol 89:11820-11833.) |
ORF10 |
|
Cullin 2 (CUL2) RING E3 ligase complex; ZYG11B |
(Gordon et al., 2020Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O’Meara MJ, Rezelj VV, Guo JZ, Swaney DL et al. (2020) A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583:459-468.) |