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Table S1. Function and structure of DENV proteins Proteins Functions and special properties Capsid Building block of the protein Structure domains N-terminus (the structural protein with the shell that encloses vRNA, forms the nucleocapsid (NC) core. most variability among the flaviviruses) Four helices (α1–α4, at aa positions V26–K35, K45–A58, A63–W69, and K74–N96, respectively) connected by short loops C-terminus (a signal sequence) PrM Chaperone for folding and Pr (~80aa): seven antiparallel β-strands assembly of the E protein (stabilized by three disulphide bonds), two helices, and two transmembrane helices furin cleavage site: Arg-X*-(Lys/Arg) -Arg M peptide (75 aa) Envelope Attachment and membrane EDIII (aa: 1–100): contains BC, DE and fusion. An E monomer FG loops and forms an Ig-like β-barrel consisting of three -barrel structure domains (EDI–III) with folds EDII (aa: 109–250): a finger-like based largely on β-sheets. The elongated structure with a hydrophobic EDIII is the receptor-binding sequence in a loop at its tip domain. The EDII is a EDI (aa: 270–439): located at the hydrophobic fusion peptide, N-terminal but with a structurally central which is sequence conserved domain connecting EDII and EDIII among all flaviviruses. NS1 An unusual viral glycoprotein two N-linked glycosylation sites not found in infectious virion. It 12 hemicystines, and a signalase-like appears in infected cells processing site at N-terminus involved in viral RNA replication and serves as a serum marker of disease severity. NS2A NS2B Forms part of the RNA Contain no conserved motifs characteristic replication complex of known enzymes. Co-factor for NS3 protease. Residues 67-80 interact with the NS3pro, flanking hydrophobic regions. 1 Table S1. Function and structure of DENV proteins (cont’d) Proteins Functions and special properties NS3 Highly conserved Structure domains NS3pro (~180 aa): consists of six β-strands multifunctional protein essential arranged into two β-barrels. The catalytic for proteolytic activity in center (His51, Asp75 and Ser135) is located N-terminus (serine between these two β-barrels. apoprotease, NS3 ) and for pro NS3hel (aa: 181–618): subdomain I RNA replication in C terminus includes motifs A, B and Ia; subdomain II hel (RNA ). includes motifs III-VI; subdomain III consists of four α-helices surrounded by three shorter α-helices and two antiparallel β-strands.. NS4A May induce membrane Contains no conserved motifs characteristic alterations needed for virus of known enzymes. replication. A small hydrophobic protein (150 aa, possibly a membrane spanning protein) with a cytoplasmic N-terminal region and rich in α-helices followed by two transmembrane domains separated by a short peptide and a short C-terminal domain. NS4B May block IFN α/β-induced A small (248 aa) hydrophobic protein signal transduction. containing no conserved motifs characteristic of known enzymes. NS5 Methyltransferase (MTase) MTase (aa: 1–269): An α/β/β sandwich responsible for capping and flanked by N-terminus and C-terminus. methylating the capped + RdRp (aa: 270–900): Composed of six ssRNA Genome on its 5’ signature-sequence motifs (A-F) and a terminus and RNA-dependent priming loop. Organized from the N RNA (RdRp). terminus to the C terminus as two nuclear localization sequences (NLS, aa: 316–368 andNLS, aa: 370–405), finger (comprises codons 273–315, 416–496, and 543–600), palm (aa: 556–639), and thumb (640–798) subdomains. *. X: any amino acid 2