Supplementary materials, information

Supplementary Table S1. List of GO terms used for the networks COVID-19, chloroquine and arrhythmia markers.

Supplementary Table S2. List of the nodes of intersection of COVID-19 and chloroquine (264 nodes) and ACE2/TMPRSS2 and chloroquine (2 nodes).

Supplementary Figure S1. Network generated with the targets of chloroquine (A) and biological processes represented by that network (B). The network was built with Cytoscape and UniProt database. Biological processes were retrieved with BiNGO tool.

Supplementary Figure S2. Network generated with the targets of COVID-19 (A) and biological processes represented by that network (B). The network was built with Cytoscape and UniProt database. Biological processes were retrieved with BiNGO tool.

Supplementary Figure S3. Network generated with the targets of ACE2 and TMPRSS2 (A) and biological processes represented by that network (B). The network was built with Cytoscape and UniProt database. Biological processes were retrieved with BiNGO tool.

Supplementary Figure S4. Network generated with the targets of arrhytmia (A) and biological processes represented by that network (B). The network was built with Cytoscape and UniProt database. Biological processes were retrieved with BiNGO tool.

Supplementary File S1. Cytoscape Session file (.cys) contains networks used in this study. These networks can be evaluated for nodes and edges of interest, e.g. to see identifiers. See the text for annotation of the networks. The file is uploaded at FigShare for free access; link is https://figshare.com/articles/online_resource/SupplementaryFileS1_Cytoscape_DataNetwork_cy s/12793580 .

Supplementary Figure S1

B A 1336 nodes, 2526 edges 1224 biological processes Supplementary Figure S2

A B 828 nodes, 1545 edges 721 biological processes Supplementary Figure S3

A B 231 biological processes 15 nodes, 19 edges Supplementary Figure S4

B A 63 nodes, 80 edges 641 biological processes Supplementary Table S1. Lists of nodes used in this study for building networks.

A) Targets of chloroquine GSTA2, TNF, TLR9, GST, HMGB1, GSTM1, CYP2C8, CYP3A4, CYP3A5, CYP2D6, CYP1A1

B) COVID-19 interacting AP3B1, BRD4, BRD2, CWC27, ZC3H18, SLC44A2, PMPCB, YIF1A, ATP1B1, ACADM, ETFA, STOM, GGCX, ATP6V1A, PSMD8, REEP5, PMPCA, ANO6, PITRM1, SLC30A9, FASTKD5, SLC30A7, TUBGCP3, COQ8B, SAAL1, REEP6 , INTS4, SLC25A21, TUBGCP2, TARS2, RTN4, FAM8A1, AASS, AKAP8L, AAR2, BZW2, RRP9, PABPC1, CSNK2A2, CSNK2B, G3BP1, PABPC4, LARP1, FAM98A, SNIP1, UPF1, MOV10, G3BP2, DDX21, RBM28, RPL36, GOLGA7, ZDHHC5, POLA1, PRIM1, PRIM2, POLA2, COLGALT1, PKP2, AP2A2, GFER, ERGIC1, AP2M1, GRPEL1, TBCA, SBNO1, BCKDK, AKAP8, MYCBP2, SLU7, RIPK1, UBAP2L, TYSND1, PDZD11, PRRC2B, UBAP2, ZNF318, CRTC3, USP54, ZC3H7A, LARP4B, RBM41, TCF12, PPIL3, PLEKHA5, TBKBP1, CIT, HSBP1, PCNT, CEP43, PRKAR2A, PRKACA, PRKAR2B, RDX, CENPF, TLE1, TLE3, TLE5, GOLGA3, GOLGA2, GOLGB1, GRIPAP1, CEP350, PDE4DIP, CEP135, CEP68, CNTRL, ERC1, GCC2, CLIP4, NIN, CEP112, MIPOL1, USP13, GCC1, JAKMIP1, CDK5RAP2, AKAP9, GORASP1, FYCO1, C1orf50, CEP250, TBK1, HOOK1, NINL, GLA, IMPDH2, SIRT5, NUTF2, ARF6, RNF41, SLC27A2, EIF4E2, POR, RAP1GDS1, WASHC4, FKBP15, GIGYF2, IDE, TIMM10, ALG11, NUP210, TIMM29, DNAJC11, TIMM10B, TIMM9, HDAC2, GPX1, TRMT1, ATP5MG, ATP6AP1, SIGMAR1, ATP13A3, AGPS, CYB5B, ACSL3, CYB5R3, RALA, COMT, RAB5C, RAB7A, RAB8A, RAB2A, RAB10, RAB14, RHOA, RAB1A, GNB1, GNG5, LMAN2, MOGS, TOR1AIP1, MTARC1, QSOX2, HS2ST1, NDUFAF2, SCCPDH, SCARB1, NAT14, DCAKD, FAM162A, DNAJC19, SELENOS, PTGES2, RAB18, MPHOSPH10, SRP72, ATE1, NSD2, SRP19, SRP54, MRPS25, DDX10, LARP7, MEPCE, NGDN, EXOSC8, NARS2, NOL10, CCDC86, SEPSECS, EXOSC5, EXOSC3, AATF, HECTD1, MRPS2, MRPS5, EXOSC2, MRPS27, GTF2F2, FBN1, FBN2, NUP214, NUP62, DCAF7, EIF4H, NUP54, MIB1, SPART, NEK9, ZNF503, NUP88, NUP58, MAT2B, FBLN5, PPT1, CUL2, MAP7D1, THTPA, ZYG11B, TIMM8B, RBX1, ELOC, ELOB, HMOX1, TRIM59, ARL6IP6, VPS39, CLCC1, VPS11, SUN2, ALG5, STOML2, NUP98, RAE1, MTCH1, HEATR3, MDN1, PLOD2, TOR1A, STC2, PLAT, ITGB1, CISD3, COL6A1, PVR, DNMT1, LOX, PCSK6, INHBE, NPC2, MFGE8, OS9, NPTX1, POGLUT2, POGLUT3, ERO1B, PLD3, FOXRED2, CHPF, PUSL1, EMC1, GGH, ERLEC1, IL17RA, NGLY1, HS6ST2, SDF2, NEU1, GDF15, TM2D3, ERP44, EDEM3, SIL1, POFUT1, SMOC1, PLEKHF2, FBXL12, UGGT2, CHPF2, ADAMTS1, HYOU1, FKBP7, ADAM9, FKBP10, SLC9A3R1, CHMP2A, CSDE1, TOMM70, MARK3, MARK2, DPH5, DCTPP1, MARK1, PTBP2, BAG5, UBXN8, GPAA1, WFS1, ABCC1, F2RL1, SCAP, DPY19L1, TMEM97, SLC30A6, TAPT1, ERMP1, NLRX1, RETREG3, PIGO, FAR2, ECSIT, ALG8, TMEM39B, GHITM, ACAD9, NDFIP2, BCS1L, NDUFAF1, TMED5, NDUFB9, PIGS

C) Markers of arrhythmia

OPN, ANXA5, GDF15, MPO, LGALS3, TNNT2, TNNI3, ANFB, REN, IL6, CRP Supplementary Table S2

Intersection nodes of Chloroquine and COVID‐19 networks.

The listed are 266 nodes that are common for the networks formed by chloroquine and COVID‐19. The rows from 3 to 266 show the nodes of COVID‐19 network, and the last 2 rows annotate ACE2/TMPRSS2 common nodes, ALB and YWHAZ.

Common nodes of Chloroquine and Covid19 networks Accession Name Human number Label P09429 High mobility group box 1 HMGB1 P12004 Proliferating cell nuclear antigen PCNA Q9Y3U8 Ribosomal L36 RPL36 Q9Y2W1 Thyroid hormone receptor associated protein 3 THRAP3 Q9NYF8 BCL2 associated transcription factor 1 BCLAF1 Q9H307 Pinin, desmosome associated protein PNN Q8NEJ9 Neuroguidin NGDN Q86VM9 Zinc finger CCCH‐type containing 18 ZC3H18 Q6PKG0 La ribonucleoprotein 1, translational regulator LARP1 Q15287 RNA binding protein with serine rich domain 1 RNPS1 Q13573 SNW domain containing 1 SNW1 Q09161 Nuclear cap binding protein subunit 1 NCBP1 P62913 Ribosomal protein L11 RPL11 P62753 Ribosomal protein S6 kinase B1 RPS6 P62424 Ribosomal protein L7A RPL7A P38919 Eukaryotic translation initiation factor 4A3 EIF4A3 P23396 Ribosomal protein S3 RPS3 P19338 Nucleolin NCL Q07021 Complement C1q binding protein C1QBP P42858 Huntingtin HTT P12682 High mobility group box 1 HMGB1 Q9QUN7 Toll like receptor 2 Tlr2 P63158 High mobility group box 1 Hmgb1 O00206 Toll like receptor 4 TLR4 Q9QUK6 Toll like receptor 4 Tlr4 Q8TDQ0 Hepatitis A virus cellular receptor 2 HAVCR2 P43405 Spleen associated tyrosine kinase SYK Q9NP31 SH2 domain containing 2A SH2D2A P60484 Phosphatase and tensin homolog PTEN CHEBI:16755 CHEBI:16755 P22366 MYD88 innate immune signal transduction adaptor Myd88 O60260 Parkin RBR E3 ubiquitin protein ligase PRKN Q7Z434 Mitochondrial antiviral signaling protein MAVS O95786 DExD/H‐box helicase 58 DDX58

1

Q9BYX4 Interferon induced with helicase C domain 1 IFIH1 O15111 Component of inhibitor of nuclear factor kappa B kinase CHUK complex O14920 Inhibitor of nuclear factor kappa B kinase subunit beta IKBKB P35637 FUS RNA binding protein FUS Q08211 DExH‐box helicase 9 DHX9 P10636‐8 associated protein tau MAPT EBI‐14348029 EBI‐ 14348029 Q05127 Polymerase complex protein VP35 Q9HCE5 Methyltransferase like 14 METTL14 Q9R1S0 B9 domain containing 1 B9d1 P55085 F2R like trypsin receptor 1 F2RL1 Q9UBU9 Nuclear RNA export factor 1 NXF1 Q28141 DExH‐box helicase 9 DHX9 P61286 Poly(A) binding protein cytoplasmic 1 PABPC1 Q9QXM1 Junction mediating and regulatory protein, p53 cofactor JMY P07602 Prosaposin PSAP Q14164 Inhibitor of nuclear factor kappa B kinase subunit epsilon IKBKE P04487 Tegument protein US11 [Human alphaherpesvirus 1 US11 Q9H7S9 Zinc finger protein 703 ZNF703 F1BA49 B303_sSgp2 nonstructural protein [ SFTS virus HB29 ] F1BA49 O75569 Protein activator of interferon induced PRKRA EIF2AK2 Q9UHD2 TANK binding kinase 1 TBK1 Q9NZ43 Unconventional SNARE in the ER 1 USE1 Q86U44 Methyltransferase like 3 METTL3 O00571 DEAD‐box helicase 3 X‐linked DDX3X O35658 Complement C1q binding protein C1qbp Q9NVI7 ATPase family AAA domain containing 3A ATAD3A Q5T9A4 ATPase family AAA domain containing 3B ATAD3B O14730 RIO kinase 3 RIOK3 O14672 ADAM metallopeptidase domain 10 ADAM10 P49768 Presenilin 1 PSEN1 P05067‐ Amyloid beta precursor protein APP PRO_0000000092 Q8N6Q3 CD177 CD177 P05067‐8 Amyloid beta precursor protein APP P49755 Transmembrane p24 trafficking protein 10 TMED10 Q8N766 ER membrane protein complex subunit 1 EMC1 Q04637 Eukaryotic translation initiation factor 4 gamma 1 EIF4G1 P54253 Ataxin 1 ATXN1 Q923E4 Sirtuin 1 Sirt1 P34902 Interleukin 2 receptor subunit gamma Il2rg

2

P07750 Interleukin 4 Il4 Q9NQC3 Reticulon 4 RTN4 Q16820 Meprin A subunit beta MEP1B O00213 Amyloid beta precursor protein binding family B member 1 APBB1 Q9Y6D5 ADP ribosylation factor guanine nucleotide exchange factor ARFGEF2 2 P19438 TNF receptor superfamily member 1A TNFRSF1A Q9ULZ3 PYD and CARD domain containing PYCARD Q13546 Receptor interacting serine/threonine kinase 1 RIPK1 P48729 Casein kinase 1 alpha 1 CSNK1A1 Q06A28 Ribonucleoside‐diphosphate reductase large subunit RIR1 Q60855 Receptor interacting serine/threonine kinase 1 Ripk1 Q9Y6K9 Inhibitor of nuclear factor kappa B kinase regulatory IKBKG subunit gamma O70343 PPARG coactivator 1 alpha Ppargc1a Q9UBK2 PPARG coactivator 1 alpha PPARGC1A Q9DBR0 A‐kinase anchoring protein 8 Akap8 P25799 Nuclear factor kappa B subunit 1 Nfkb1 O43823 A‐kinase anchoring protein 8 AKAP8 P42574 Caspase 3 CASP3 Q12933 TNF receptor associated factor 2 TRAF2 Q9UQ80 Proliferation‐associated 2G4 PA2G4 Q92769 Histone deacetylase 2 HDAC2 Q9Z2D8 Methyl‐CpG binding domain protein 3 Mbd3 Q6NYC1 Jumonji domain containing 6, arginine demethylase and JMJD6 lysine hydroxylase P04156 Prion protein PRNP Q06124 Protein tyrosine phosphatase non‐receptor type 11 PTPN11 Q01101 INSM transcriptional repressor 1 INSM1 O88895 Histone deacetylase 3 Hdac3 P25322 Cyclin D1 Ccnd1 P70288 Histone deacetylase 2 Hdac2 E9QAG8 Zinc finger protein 431 Znf431 Q2HR82 K8 Q13547 Histone deacetylase 1 HDAC1 Q9UL18 Argonaute RISC component 1 AGO1 Q9UKV8 Argonaute RISC catalytic component 2 AGO2 P29317 EPH receptor A2 EPHA2 Q8IUC6 Toll like receptor adaptor molecule 1 TICAM1 Q9UI95 Mitotic arrest deficient 2 like 2 MAD2L2 Q3URK3 TET methylcytosine dioxygenase 1 Tet1 P09651 Heterogeneous nuclear ribonucleoprotein A1 HNRNPA1 O75376 Nuclear receptor corepressor 1 NCOR1

3

O75469 Nuclear receptor subfamily 1 group I member 2 NR1I2 Q96EB6 Sirtuin 1 SIRT1 Q15831 Serine/threonine kinase 11 STK11 Q09472 E1A binding protein p300 EP300 Q9Z0Y9 Nuclear receptor subfamily 1 group H member 3 Nr1h3 Q60644 Nuclear receptor subfamily 1 group H member 2 Nr1h2 P06400 RB transcriptional corepressor 1, pRb RB1 Q99417 MYC binding protein MYCBP P31323 Protein kinase cAMP‐dependent type II regulatory subunit PRKAR2B beta Q8R4A3 Dishevelled binding antagonist of beta catenin 1 Dact1 Q7TN08 Dishevelled binding antagonist of beta catenin 2 Dact2 O70237 Growth factor independent 1B transcriptional repressor Gfi1b P70338 Growth factor independent 1 transcriptional repressor Gfi1 O43463 Suppressor of variegation 3‐9 homolog 1 SUV39H1 Q9UIS9 Methyl‐CpG binding domain protein 1 MBD1 P68400 Casein kinase 2 alpha 1 CSNK2A1 Q9ERZ6 Fidgetin, microtubule severing factor Fign P17612 Protein kinase cAMP‐activated catalytic subunit alpha PRKACA Q61656 DExD/H‐box helicase 58 Ddx5 Q63014 A‐kinase anchoring protein 8 Akap8 Q15418 Ribosomal protein S6 kinase A1 RPS6KA1 P18653 Ribosomal protein S6 kinase A1 Rps6ka1 P42574‐ Caspase 3 CASP3 PRO_0000004572 P42574‐ Caspase 3 CASP3 PRO_0000004571 P49736 Minichromosome maintenance complex component 2 MCM2 O15379 Histone deacetylase 3 HDAC3 Q9ULX6 A‐kinase anchoring protein 8 like AKAP8L Q96GD4 Aurora kinase B AURKB Q9Y618 Nuclear receptor corepressor 2 NCOR2 P78371 Chaperonin containing TCP1 subunit 2 CCT2 Q9P2S5 WD repeat containing, antisense to TP73 WRAP73 Q9Y2D8 SSX family member 2 interacting protein SSX2IP P13861 Protein kinase cAMP‐dependent type II regulatory subunit PRKAR2A alpha P24385 Cyclin D1 CCND1 Q15021 non‐SMC condensin I complex subunit D2 NCAPD2 Q8CJG0 Argonaute RISC catalytic component 2 Ago2 Q14964 Member RAS oncogene family RAB39A Q8NFZ5 TNFAIP3 interacting protein 2 TNIP2 Q8WV41 Sorting nexin 33 SNX33 Q9Y5X1 Sorting nexin 9 SNX9

4

P42680 Tectorin alpha TEC P14598 Neutrophil cytosolic factor 1 NCF1 Q96RF0 Sorting nexin 18 SNX18 P22893 ZFP36 ring finger protein like 1 Zfp36 P25963 NFKB inhibitor alpha NFKBIA O75509 TNF receptor superfamily member 21 TNFRSF21 Q9HCE1 Mov10 RISC complex RNA helicase MOV10 P11940 Poly(A) binding protein cytoplasmic 1 PABPC1 P50402 Emerin EMD P52298 Nuclear cap binding protein subunit 2 NCBP2 Q06265 Exosome component 9 EXOSC9 Q96PU4 Ubiquitin like with PHD and ring finger domains 2 UHRF2 P21926 CD9 molecule, tetraspanin CD9 P78536 ADAM metallopeptidase domain 17 ADAM17 P62079 Tetraspanin 5 TSPAN5 O95858 Tetraspanin 15 TSPAN15 P06756 Integrin subunit alpha V ITGAV P05556 Integrin subunit beta 1 ITGB1 O95859 Tetraspanin 12 TSPAN12 Q9BY11 Protein kinase C and casein kinase substrate in neurons 1 PACSIN1 Q9UNF0 Protein kinase C and casein kinase substrate in neurons 2 PACSIN2 Q9UKS6 Protein kinase C and casein kinase substrate in neurons 2 PACSIN3 P03129 E7 transforming protein Human papillomavirus E7 Q8B5B5 E7 transforming protein Human papillomavirus E7 Q07857 E7 transforming protein Human papillomavirus E7 Q80901 E7 transforming protein Human papillomavirus E7 Q6TY35 E7 transforming protein Human papillomavirus E7 Q6TY28 E7 transforming protein Human papillomavirus E7 Q80908 E7 transforming protein Human papillomavirus E7 P50778 E7 transforming protein Human papillomavirus E7 Q92985 Interferon regulatory factor 7 IRF7 Q77M20 Phosphoprotein, Measles virus strain Schwarz P Q77M19 Phosphoprotein, Measles virus strain Schwarz P Q92900‐2 UPF1 RNA helicase and ATPase UPF1 P24772 hypothetical protein VACWR196 [Vaccinia virus] VACWR196 Q9Y6Q9 Nuclear receptor coactivator 3 NCOA3 Q92793 CREB binding protein CREBBP Q13257 Mitotic arrest deficient 2 like 1 MAD2L1 P46940 IQ motif containing GTPase activating protein 1 IQGAP1 P42704 Leucine rich pentatricopeptide repeat containing LRPPRC Q6PB66 Leucine rich pentatricopeptide repeat containing Lrpprc Q9UKV0‐7 Histone deacetylase 9 HDAC9 Q9UKV0‐3 Histone deacetylase 9 HDAC9

5

P05067 Amyloid Precursor Protein APP Q86SQ7 SHH signaling and ciliogenesis regulator SDCCAG8 SDCCAG8 P10636 Microtubule associated protein tau MAPT P08138 Nerve growth factor receptor NGFR O95070 Yip1 interacting factor homolog A, membrane trafficking YIF1A protein Q5BJF2 Transmembrane protein 97 TMEM97 Q99720 Sigma non‐opioid intracellular receptor 1 SIGMAR1 P21964 Catechol‐O‐methyltransferase COMT P35613 Basigin (Ok blood group) BSG O88351 Inhibitor of nuclear factor kappa B kinase subunit beta Ikbkb P14340 Polyprotein, viral capsid? P14340 Q9H6S1 5‐azacytidine induced 2 AZI2 P17362 C6L hypothetical protein [ Vaccinia virus ] VACWR022 Q92844 TRAF family member associated NFKB activator TANK Q9NZN8 CCR4‐NOT transcription complex subunit 2 CNOT2 Q13227 G protein pathway suppressor 2 GPS2 P17020 Zinc finger protein 16 ZNF16 P15090 Fatty acid binding protein 4 FABP4 Q60680 Component of inhibitor of nuclear factor kappa B kinase Chuk complex Q9Y5K5 Ubiquitin C‐terminal hydrolase L5 UCHL5 P48556 Proteasome 26S subunit, non‐ATPase 8 PSMD8 O60826 Coiled‐coil domain containing 22 CCDC22 Q14676 Mediator of DNA damage checkpoint 1 MDC1 Q6ZNX1 Shieldin complex subunit 3 SHLD3 P03372 Estrogen receptor 1 ESR1 P10085 Myogenic differentiation 1 Myod1 Q15363 Transmembrane p24 trafficking protein 2 TMED2 P22681 Cbl proto‐oncogene CBL O88522 Inhibitor of nuclear factor kappa B kinase regulatory Ikbkg subunit gamma Q92905 COP9 signalosome subunit 5 COPS5 Q63645 F2R like trypsin receptor 1 F2rl1 Q63524 Transmembrane p24 trafficking protein 2 Tmed2 Q14868 Homeodomain‐like superfamily protein EPR‐1 O43889‐2 cAMP responsive element binding protein 3 CREB3 Q92831 Lysine acetyltransferase 2B KAT2B EBI‐5261640 Sirtuin 1 Sirt1 Q9QYK2 PPARG coactivator 1 alpha Ppargc1a Q9NS37 CREB/ATF bZIP transcription factor CREBZF Q04724 TLE family member 1, transcriptional corepressor TLE1 P98078 DAB adaptor protein 2 Dab2

6

Q14781 Chromobox 2 CBX2 Q9HC52 Chromobox 8 CBX8 Q12888 Tumor protein p53 binding protein 1 TP53BP1 Q02241 Kinesin family member 23 KIF23 Q92945 KH‐type splicing regulatory protein KHSRP P17813 Endoglin ENG P19784 Casein kinase 2 alpha 2 CSNK2A2 P26358 DNA methyltransferase 1 DNMT1 O95905 Ecdysoneless regulator ECD A2AG06 Meiosis specific with coiled‐coil domain Meioc Q96RI1‐2 Nuclear receptor subfamily 1 group H member 4 NR1H4 P02786 Transferrin receptor TFRC Q08431 Milk fat globule EGF and factor V/VIII domain containing MFGE8 P61006 RAB8A, member RAS oncogene family RAB8A Q8IVH8 Mitogen‐activated protein kinase kinase kinase kinase 3 MAP4K3 Q13443 ADAM metallopeptidase domain 9 ADAM9 O94875 Sorbin and SH3 domain containing 2 SORBS2 P13639 Eukaryotic translation elongation factor 2 EEF2 P03206 protein Zta [Human gammaherpesvirus 4 (Epstein‐Barr BZLF1 virus)] Q8IZ52‐2 Chondroitin polymerizing factor CHPF O60346 PH domain and leucine rich repeat protein phosphatase 1 PHLPP1 P62136 Protein phosphatase 1 catalytic subunit alpha PPP1CA Q9JKL7 Splicing regulatory glutamic acid and lysine rich protein 1 Srek1 Q99962 SH3 domain containing GRB2 like 2, endophilin A1 SH3GL2 Q61072 ADAM metallopeptidase domain 9 Adam9 Q99JB8 Protein kinase C and casein kinase substrate in neurons 2 Pacsin3 Q62420 SH3 domain containing GRB2 like 2, endophilin A1 Sh3gl2 Common nodes of ACE2/TPMRSS2 and chloroquine networks P02768 Albumin ALB P63101 14‐3‐3‐zeta, YWHAZ – tyrosine 3‐ YWHAZ monooxygenase/tryptophan 5‐monooxygenase activation protein zeta

7