CODSWALLOP

Replicase polyprotein 1ab

Severe acute respiratory syndrome coronavirus 2 · seed P0DTD1 · 7096 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

1,960Entries 2,000Entities 252Constructs 7Organisms 1,624Ligand-bound
1.16 ÅBest res.
1.92 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

9M29, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 9M29
9M29 at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

1354870961351 constructs

Constructs, most-used first

252 distinct constructs across 1,960 entries. 2,000 polymer entities differ from the UniProt canonical sequence in some way, 16 carry a recognised expression tag and 0 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
953 306 1.16 9ZNL residues 3264-3569
128 354 1.68 13RB residues 1536-1880; 9-residue insertion after 1560; Y1536M, Y1537G, T1538S +20 more
70 601 1.79 5RL9 residues 5325-5925
68 523 1.58 5SLD residues 5930-6452; T5930S, G5931M
57 309 1.45 7T44 residues 3260-3568; A3260S, V3261N, L3262I +1 more
39 932 2.58 9DJ8 residues 4393-5324
32 349 1.64 5SBF residues 6450-6798; R6450G, L6451A, Q6452M
26 305 1.25 6YB7 residues 3264-3568
25 317 1.71 9M9B residues 1563-1879; R1563M, E1564A, C1674S
24 318 1.79 6WZU residues 1561-1878; L1562N, R1563A
20 318 1.60 6WRH residues 1561-1878; L1562N, R1563A, C1674S
18 306 1.70 7S74 residues 3264-3569; E3441A
15 306 1.62 7MB8 residues 3264-3569; C3408A
15 523 1.84 9QXB residues 5930-6452; G5931M
13 306 1.50 8DI3 residues 3264-3569; P3395H
13 307 1.25 7JKV residues 3263-3569; Q3263G
11 308 1.35 9AT4 residues 3260-3567; A3260S, V3261N, L3262I +1 more
11 315 1.42 7NFV residues 1564-1878
10 605 2.91 7RE1 residues 5318-5925; 1 internal deletion; T5318G, Q5324M
9 301 1.50 9SSN residues 3264-3564
9 306 1.46 8H3G residues 3264-3569; E3429V
8 306 1.49 7DVW residues 3264-3569; H3304A
8 316 1.89 9WON residues 1563-1878; R1563S
8 370 1.82 6WLC residues 6410-6798; 3 internal deletions; R6410M, A6413H, N6414H +12 more
7 525 2.29 9SAL residues 5926-6450; D6015A, E6017A

Showing the 25 most-used of 252.

What it assembles into

Oligomeric stateChainsEntriesShare
dimeric2 1,314 67.0%
monomeric1 420 21.4%
hexameric6 75 3.8%
tetrameric4 70 3.6%
octameric8 17 0.9%
trimeric3 13 0.7%
pentameric5 12 0.6%
nonameric9 12 0.6%

1,531 entries have the depositor's assembly corroborated by PISA, 414 carry the depositor's word alone and 13 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 4 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 6XG3, 8WZ0, 9J8T, 9J8U.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHSCOP2B135487096
DomainSourceSpan (seed)Chains
Trypsin-like serine proteasesCATH 2.40.10.10 3274–3354 624
main proteinase (3clpro) structure, domain 3CATH 1.10.1840.10 3464–3564 520
P-loop containing nucleotide triphosphate hydrolasesCATH 3.40.50.300 5768–5908 76
Ubiquitin-likeSCOP2B 8092569 1600–1656 254
PLpro Zn-binding domain-likeSCOP2B 8092568 1773–1836 254
Cysteine proteinasesSCOP2B 8092567 1803–1872 510
Trypsin-like serine proteasesSCOP2B 8092431 3264–3453 1,234
Nucleotide cyclase/DNA polymerase palm domain-likeSCOP2B 8092559 5071–5196 144
S-adenosyl-L-methionine-dependent methyltransferasesSCOP2B 8092436 6456–6645 59
EndoU-likeSCOP2B 8092437 6646–6801 59

What binds it

4WI 4WI33 entries ADP ADP13 entries K36 K3611 entries V2M V2M11 entries UED UED10 entries 1N7 1N710 entries 7ON 7ON9 entries AF3 AF39 entries X77 X778 entries ALD ALD8 entries SAH SAH7 entries O6K O6K7 entries
ComponentClassNameEntriesBest (Å)
DMScryoprotectant Dimethyl Sulfoxide 623 1.18
ZNion Zinc Ion 548 1.20
CLion Chloride Ion 348 1.25
PO4ion Phosphate Ion 175 1.42
NAion Sodium Ion 129 1.20
MLIbuffer Malonate Ion 107 1.65
EDOcryoprotectant 1,2-Ethanediol 95 1.20
GOLcryoprotectant Glycerol 94 1.31
MGion Magnesium Ion 71 1.47
SO4ion Sulfate Ion 46 1.39
PG4cryoprotectant Tetraethylene Glycol 39 1.31
PEGcryoprotectant Di(Hydroxyethyl)ether 37 1.25
4WIligand (1r,2s,5s)-N-{(1e,2s)-1-Imino-3-[(3s)-2-Oxopyrrolidin-3-Yl]propa 33 1.49
ACTcryoprotectant Acetate Ion 28 1.28
IMDbuffer Imidazole 20 1.40
CITbuffer Citric Acid 18 1.64
FMTbuffer Formic Acid 14 1.28
ADPcofactor Adenosine-5'-Diphosphate 13 1.82
7YYbuffer 6-[(6-Chloranyl-2-Methyl-Indazol-5-Yl)amino]-3-[(1-Methyl-1,2,4- 12 1.46
K36ligand (1s,2s)-2-({N-[(Benzyloxy)carbonyl]-L-Leucyl}amino)-1-Hydroxy-3- 11 1.35

How it crystallises

Parsed from the free text 1,834 depositors typed into _exptl_crystal_grow.pdbx_details, out of 1,834 entries that recorded anything at all. Median pH 6.5 (range 3.5 to 9.0).

Precipitants

PEG × Ammonium sulfate × Sodium chloride × Ammonium phosphate × Sodium malonate × Sodium citrate × MPD × Magnesium chloride × Isopropanol × Sodium formate × Lithium sulfate × Tacsimate × PEG (unspecified) × Calcium chloride ×

Buffers

MES × HEPES × Bis-Tris × Phosphate × Tris × Imidazole × Citrate × Bis-Tris propane × Sodium acetate × Sodium cacodylate × Glycine × Succinate ×

Which entries to trust

1,953 entries carry a wwPDB validation report: 941 clean, 855 worth a check and 157 with something to explain. Median clashscore 3.59, median RSRZ outliers 4.93%, median R-free minus R-work 0.038. 1,953 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Severe acute respiratory syndrome coronavirus 21,932 1.16 1606 89%
Severe acute respiratory syndrome coronavirus13 1.50 13 12%
Severe acute respiratory syndrome-related coronavirus7 2.71 2 36%
SARS-CoV-2 pseudovirus3 2.18 3 7%
Unknown2 0 17%
Homo sapiens1 2.05 0 4%
Human betacoronavirus 2c EMC/20121 3.00 0 8%
SARS coronavirus Frankfurt 11 3.38 0 7%

Seed sequence

7096 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

1MESLVPGFNE KTHVQLSLPV LQVRDVLVRG FGDSVEEVLS EARQHLKDGT CGLVEVEKGV
61LPQLEQPYVF IKRSDARTAP HGHVMVELVA ELEGIQYGRS GETLGVLVPH VGEIPVAYRK
121VLLRKNGNKG AGGHSYGADL KSFDLGDELG TDPYEDFQEN WNTKHSSGVT RELMRELNGG
181AYTRYVDNNF CGPDGYPLEC IKDLLARAGK ASCTLSEQLD FIDTKRGVYC CREHEHEIAW
241YTERSEKSYE LQTPFEIKLA KKFDTFNGEC PNFVFPLNSI IKTIQPRVEK KKLDGFMGRI
301RSVYPVASPN ECNQMCLSTL MKCDHCGETS WQTGDFVKAT CEFCGTENLT KEGATTCGYL
361PQNAVVKIYC PACHNSEVGP EHSLAEYHNE SGLKTILRKG GRTIAFGGCV FSYVGCHNKC
421AYWVPRASAN IGCNHTGVVG EGSEGLNDNL LEILQKEKVN INIVGDFKLN EEIAIILASF
481SASTSAFVET VKGLDYKAFK QIVESCGNFK VTKGKAKKGA WNIGEQKSIL SPLYAFASEA
541ARVVRSIFSR TLETAQNSVR VLQKAAITIL DGISQYSLRL IDAMMFTSDL ATNNLVVMAY
601ITGGVVQLTS QWLTNIFGTV YEKLKPVLDW LEEKFKEGVE FLRDGWEIVK FISTCACEIV
661GGQIVTCAKE IKESVQTFFK LVNKFLALCA DSIIIGGAKL KALNLGETFV THSKGLYRKC
721VKSREETGLL MPLKAPKEII FLEGETLPTE VLTEEVVLKT GDLQPLEQPT SEAVEAPLVG
781TPVCINGLML LEIKDTEKYC ALAPNMMVTN NTFTLKGGAP TKVTFGDDTV IEVQGYKSVN
841ITFELDERID KVLNEKCSAY TVELGTEVNE FACVVADAVI KTLQPVSELL TPLGIDLDEW
901SMATYYLFDE SGEFKLASHM YCSFYPPDED EEEGDCEEEE FEPSTQYEYG TEDDYQGKPL
961EFGATSAALQ PEEEQEEDWL DDDSQQTVGQ QDGSEDNQTT TIQTIVEVQP QLEMELTPVV
1021QTIEVNSFSG YLKLTDNVYI KNADIVEEAK KVKPTVVVNA ANVYLKHGGG VAGALNKATN
1081NAMQVESDDY IATNGPLKVG GSCVLSGHNL AKHCLHVVGP NVNKGEDIQL LKSAYENFNQ
1141HEVLLAPLLS AGIFGADPIH SLRVCVDTVR TNVYLAVFDK NLYDKLVSSF LEMKSEKQVE
1201QKIAEIPKEE VKPFITESKP SVEQRKQDDK KIKACVEEVT TTLEETKFLT ENLLLYIDIN
1261GNLHPDSATL VSDIDITFLK KDAPYIVGDV VQEGVLTAVV IPTKKAGGTT EMLAKALRKV
1321PTDNYITTYP GQGLNGYTVE EAKTVLKKCK SAFYILPSII SNEKQEILGT VSWNLREMLA
1381HAEETRKLMP VCVETKAIVS TIQRKYKGIK IQEGVVDYGA RFYFYTSKTT VASLINTLND
1441LNETLVTMPL GYVTHGLNLE EAARYMRSLK VPATVSVSSP DAVTAYNGYL TSSSKTPEEH
1501FIETISLAGS YKDWSYSGQS TQLGIEFLKR GDKSVYYTSN PTTFHLDGEV ITFDNLKTLL
1561SLREVRTIKV FTTVDNINLH TQVVDMSMTY GQQFGPTYLD GADVTKIKPH NSHEGKTFYV
1621LPNDDTLRVE AFEYYHTTDP SFLGRYMSAL NHTKKWKYPQ VNGLTSIKWA DNNCYLATAL
1681LTLQQIELKF NPPALQDAYY RARAGEAANF CALILAYCNK TVGELGDVRE TMSYLFQHAN
1741LDSCKRVLNV VCKTCGQQQT TLKGVEAVMY MGTLSYEQFK KGVQIPCTCG KQATKYLVQQ
1801ESPFVMMSAP PAQYELKHGT FTCASEYTGN YQCGHYKHIT SKETLYCIDG ALLTKSSEYK
1861GPITDVFYKE NSYTTTIKPV TYKLDGVVCT EIDPKLDNYY KKDNSYFTEQ PIDLVPNQPY
1921PNASFDNFKF VCDNIKFADD LNQLTGYKKP ASRELKVTFF PDLNGDVVAI DYKHYTPSFK
1981KGAKLLHKPI VWHVNNATNK ATYKPNTWCI RCLWSTKPVE TSNSFDVLKS EDAQGMDNLA
2041CEDLKPVSEE VVENPTIQKD VLECNVKTTE VVGDIILKPA NNSLKITEEV GHTDLMAAYV
2101DNSSLTIKKP NELSRVLGLK TLATHGLAAV NSVPWDTIAN YAKPFLNKVV STTTNIVTRC
2161LNRVCTNYMP YFFTLLLQLC TFTRSTNSRI KASMPTTIAK NTVKSVGKFC LEASFNYLKS
2221PNFSKLINII IWFLLLSVCL GSLIYSTAAL GVLMSNLGMP SYCTGYREGY LNSTNVTIAT
2281YCTGSIPCSV CLSGLDSLDT YPSLETIQIT ISSFKWDLTA FGLVAEWFLA YILFTRFFYV
2341LGLAAIMQLF FSYFAVHFIS NSWLMWLIIN LVQMAPISAM VRMYIFFASF YYVWKSYVHV
2401VDGCNSSTCM MCYKRNRATR VECTTIVNGV RRSFYVYANG GKGFCKLHNW NCVNCDTFCA
2461GSTFISDEVA RDLSLQFKRP INPTDQSSYI VDSVTVKNGS IHLYFDKAGQ KTYERHSLSH
2521FVNLDNLRAN NTKGSLPINV IVFDGKSKCE ESSAKSASVY YSQLMCQPIL LLDQALVSDV
2581GDSAEVAVKM FDAYVNTFSS TFNVPMEKLK TLVATAEAEL AKNVSLDNVL STFISAARQG
2641FVDSDVETKD VVECLKLSHQ SDIEVTGDSC NNYMLTYNKV ENMTPRDLGA CIDCSARHIN
2701AQVAKSHNIA LIWNVKDFMS LSEQLRKQIR SAAKKNNLPF KLTCATTRQV VNVVTTKIAL
2761KGGKIVNNWL KQLIKVTLVF LFVAAIFYLI TPVHVMSKHT DFSSEIIGYK AIDGGVTRDI
2821ASTDTCFANK HADFDTWFSQ RGGSYTNDKA CPLIAAVITR EVGFVVPGLP GTILRTTNGD
2881FLHFLPRVFS AVGNICYTPS KLIEYTDFAT SACVLAAECT IFKDASGKPV PYCYDTNVLE
2941GSVAYESLRP DTRYVLMDGS IIQFPNTYLE GSVRVVTTFD SEYCRHGTCE RSEAGVCVST
3001SGRWVLNNDY YRSLPGVFCG VDAVNLLTNM FTPLIQPIGA LDISASIVAG GIVAIVVTCL
3061AYYFMRFRRA FGEYSHVVAF NTLLFLMSFT VLCLTPVYSF LPGVYSVIYL YLTFYLTNDV
3121SFLAHIQWMV MFTPLVPFWI TIAYIICIST KHFYWFFSNY LKRRVVFNGV SFSTFEEAAL
3181CTFLLNKEMY LKLRSDVLLP LTQYNRYLAL YNKYKYFSGA MDTTSYREAA CCHLAKALND
3241FSNSGSDVLY QPPQTSITSA VLQSGFRKMA FPSGKVEGCM VQVTCGTTTL NGLWLDDVVY
3301CPRHVICTSE DMLNPNYEDL LIRKSNHNFL VQAGNVQLRV IGHSMQNCVL KLKVDTANPK
3361TPKYKFVRIQ PGQTFSVLAC YNGSPSGVYQ CAMRPNFTIK GSFLNGSCGS VGFNIDYDCV
3421SFCYMHHMEL PTGVHAGTDL EGNFYGPFVD RQTAQAAGTD TTITVNVLAW LYAAVINGDR
3481WFLNRFTTTL NDFNLVAMKY NYEPLTQDHV DILGPLSAQT GIAVLDMCAS LKELLQNGMN
3541GRTILGSALL EDEFTPFDVV RQCSGVTFQS AVKRTIKGTH HWLLLTILTS LLVLVQSTQW
3601SLFFFLYENA FLPFAMGIIA MSAFAMMFVK HKHAFLCLFL LPSLATVAYF NMVYMPASWV
3661MRIMTWLDMV DTSLSGFKLK DCVMYASAVV LLILMTARTV YDDGARRVWT LMNVLTLVYK
3721VYYGNALDQA ISMWALIISV TSNYSGVVTT VMFLARGIVF MCVEYCPIFF ITGNTLQCIM
3781LVYCFLGYFC TCYFGLFCLL NRYFRLTLGV YDYLVSTQEF RYMNSQGLLP PKNSIDAFKL
3841NIKLLGVGGK PCIKVATVQS KMSDVKCTSV VLLSVLQQLR VESSSKLWAQ CVQLHNDILL
3901AKDTTEAFEK MVSLLSVLLS MQGAVDINKL CEEMLDNRAT LQAIASEFSS LPSYAAFATA
3961QEAYEQAVAN GDSEVVLKKL KKSLNVAKSE FDRDAAMQRK LEKMADQAMT QMYKQARSED
4021KRAKVTSAMQ TMLFTMLRKL DNDALNNIIN NARDGCVPLN IIPLTTAAKL MVVIPDYNTY
4081KNTCDGTTFT YASALWEIQQ VVDADSKIVQ LSEISMDNSP NLAWPLIVTA LRANSAVKLQ
4141NNELSPVALR QMSCAAGTTQ TACTDDNALA YYNTTKGGRF VLALLSDLQD LKWARFPKSD
4201GTGTIYTELE PPCRFVTDTP KGPKVKYLYF IKGLNNLNRG MVLGSLAATV RLQAGNATEV
4261PANSTVLSFC AFAVDAAKAY KDYLASGGQP ITNCVKMLCT HTGTGQAITV TPEANMDQES
4321FGGASCCLYC RCHIDHPNPK GFCDLKGKYV QIPTTCANDP VGFTLKNTVC TVCGMWKGYG
4381CSCDQLREPM LQSADAQSFL NRVCGVSAAR LTPCGTGTST DVVYRAFDIY NDKVAGFAKF
4441LKTNCCRFQE KDEDDNLIDS YFVVKRHTFS NYQHEETIYN LLKDCPAVAK HDFFKFRIDG
4501DMVPHISRQR LTKYTMADLV YALRHFDEGN CDTLKEILVT YNCCDDDYFN KKDWYDFVEN
4561PDILRVYANL GERVRQALLK TVQFCDAMRN AGIVGVLTLD NQDLNGNWYD FGDFIQTTPG
4621SGVPVVDSYY SLLMPILTLT RALTAESHVD TDLTKPYIKW DLLKYDFTEE RLKLFDRYFK
4681YWDQTYHPNC VNCLDDRCIL HCANFNVLFS TVFPPTSFGP LVRKIFVDGV PFVVSTGYHF
4741RELGVVHNQD VNLHSSRLSF KELLVYAADP AMHAASGNLL LDKRTTCFSV AALTNNVAFQ
4801TVKPGNFNKD FYDFAVSKGF FKEGSSVELK HFFFAQDGNA AISDYDYYRY NLPTMCDIRQ
4861LLFVVEVVDK YFDCYDGGCI NANQVIVNNL DKSAGFPFNK WGKARLYYDS MSYEDQDALF
4921AYTKRNVIPT ITQMNLKYAI SAKNRARTVA GVSICSTMTN RQFHQKLLKS IAATRGATVV
4981IGTSKFYGGW HNMLKTVYSD VENPHLMGWD YPKCDRAMPN MLRIMASLVL ARKHTTCCSL
5041SHRFYRLANE CAQVLSEMVM CGGSLYVKPG GTSSGDATTA YANSVFNICQ AVTANVNALL
5101STDGNKIADK YVRNLQHRLY ECLYRNRDVD TDFVNEFYAY LRKHFSMMIL SDDAVVCFNS
5161TYASQGLVAS IKNFKSVLYY QNNVFMSEAK CWTETDLTKG PHEFCSQHTM LVKQGDDYVY
5221LPYPDPSRIL GAGCFVDDIV KTDGTLMIER FVSLAIDAYP LTKHPNQEYA DVFHLYLQYI
5281RKLHDELTGH MLDMYSVMLT NDNTSRYWEP EFYEAMYTPH TVLQAVGACV LCNSQTSLRC
5341GACIRRPFLC CKCCYDHVIS TSHKLVLSVN PYVCNAPGCD VTDVTQLYLG GMSYYCKSHK
5401PPISFPLCAN GQVFGLYKNT CVGSDNVTDF NAIATCDWTN AGDYILANTC TERLKLFAAE
5461TLKATEETFK LSYGIATVRE VLSDRELHLS WEVGKPRPPL NRNYVFTGYR VTKNSKVQIG
5521EYTFEKGDYG DAVVYRGTTT YKLNVGDYFV LTSHTVMPLS APTLVPQEHY VRITGLYPTL
5581NISDEFSSNV ANYQKVGMQK YSTLQGPPGT GKSHFAIGLA LYYPSARIVY TACSHAAVDA
5641LCEKALKYLP IDKCSRIIPA RARVECFDKF KVNSTLEQYV FCTVNALPET TADIVVFDEI
5701SMATNYDLSV VNARLRAKHY VYIGDPAQLP APRTLLTKGT LEPEYFNSVC RLMKTIGPDM
5761FLGTCRRCPA EIVDTVSALV YDNKLKAHKD KSAQCFKMFY KGVITHDVSS AINRPQIGVV
5821REFLTRNPAW RKAVFISPYN SQNAVASKIL GLPTQTVDSS QGSEYDYVIF TQTTETAHSC
5881NVNRFNVAIT RAKVGILCIM SDRDLYDKLQ FTSLEIPRRN VATLQAENVT GLFKDCSKVI
5941TGLHPTQAPT HLSVDTKFKT EGLCVDIPGI PKDMTYRRLI SMMGFKMNYQ VNGYPNMFIT
6001REEAIRHVRA WIGFDVEGCH ATREAVGTNL PLQLGFSTGV NLVAVPTGYV DTPNNTDFSR
6061VSAKPPPGDQ FKHLIPLMYK GLPWNVVRIK IVQMLSDTLK NLSDRVVFVL WAHGFELTSM
6121KYFVKIGPER TCCLCDRRAT CFSTASDTYA CWHHSIGFDY VYNPFMIDVQ QWGFTGNLQS
6181NHDLYCQVHG NAHVASCDAI MTRCLAVHEC FVKRVDWTIE YPIIGDELKI NAACRKVQHM
6241VVKAALLADK FPVLHDIGNP KAIKCVPQAD VEWKFYDAQP CSDKAYKIEE LFYSYATHSD
6301KFTDGVCLFW NCNVDRYPAN SIVCRFDTRV LSNLNLPGCD GGSLYVNKHA FHTPAFDKSA
6361FVNLKQLPFF YYSDSPCESH GKQVVSDIDY VPLKSATCIT RCNLGGAVCR HHANEYRLYL
6421DAYNMMISAG FSLWVYKQFD TYNLWNTFTR LQSLENVAFN VVNKGHFDGQ QGEVPVSIIN
6481NTVYTKVDGV DVELFENKTT LPVNVAFELW AKRNIKPVPE VKILNNLGVD IAANTVIWDY
6541KRDAPAHIST IGVCSMTDIA KKPTETICAP LTVFFDGRVD GQVDLFRNAR NGVLITEGSV
6601KGLQPSVGPK QASLNGVTLI GEAVKTQFNY YKKVDGVVQQ LPETYFTQSR NLQEFKPRSQ
6661MEIDFLELAM DEFIERYKLE GYAFEHIVYG DFSHSQLGGL HLLIGLAKRF KESPFELEDF
6721IPMDSTVKNY FITDAQTGSS KCVCSVIDLL LDDFVEIIKS QDLSVVSKVV KVTIDYTEIS
6781FMLWCKDGHV ETFYPKLQSS QAWQPGVAMP NLYKMQRMLL EKCDLQNYGD SATLPKGIMM
6841NVAKYTQLCQ YLNTLTLAVP YNMRVIHFGA GSDKGVAPGT AVLRQWLPTG TLLVDSDLND
6901FVSDADSTLI GDCATVHTAN KWDLIISDMY DPKTKNVTKE NDSKEGFFTY ICGFIQQKLA
6961LGGSVAIKIT EHSWNADLYK LMGHFAWWTA FVTNVNASSS EAFLIGCNYL GKPREQIDGY
7021VMHANYIFWR NTNPIQLSSY SLFDMSKFPL KLRGTAVMSL KEGQINDMIL SLLSKGRLII
7081RENNRVVISS DVLVNN

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 Statistical crystallography reveals an allosteric network in SARS-CoV-2 M pro. Commun Biol doi:10.1038/s42003-026-10127-w
2026 Discovery of Fragment-Based Inhibitors of SARS-CoV-2 PL Pro . J.Med.Chem. doi:10.1021/acs.jmedchem.5c02832
2026 From Inhibitor to Reporter: Nirmatrelvir-Derived Fluorogenic Substrates for the SARS-CoV-2 Main Protease. Acs Chem.Biol. doi:10.1021/acschembio.6c00577
2026 Structure-based macrocyclization of alpha-ketoamides leads to potent inhibitors of coronaviral and enteroviral proteases. Commun Chem doi:10.1038/s42004-026-02151-y
2026 Structure-guided design of broad-spectrum inhibitors of coronaviral proteases embodying a 1,3,2-oxazaphospholidin-3-one scaffold as a versatile design element. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2026.119002
2026 Broad-Spectrum Peptidomimetic Inhibitors of Norovirus and Coronavirus 3C-like Proteases. Acs Infect Dis. doi:10.1021/acsinfecdis.5c00680
2026 Thiazolyl 4-carboxylate ketone as a new warhead for a highly potent SARS-CoV-2 main protease inhibitor. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.118436
2026 Enhanced Target Binding by Leritrelvir Restores Dimerization of M<sup>pro</sup> Mutants and Mitigates Drug Resistance Biorxiv doi:10.64898/2026.06.09.730104
2026 Discovery of Spiro[chromane-2,4'-piperidine] Derivatives as Irreversible Inhibitors of SARS-CoV-2 Papain-like Protease. J.Med.Chem. doi:10.1021/acs.jmedchem.5c03704
2026 Crystallographic fragment screening discovers novel micromolar active inhibitors and druggable hotspots of SARS-CoV-2 PL pro. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2026.150689
2026 A Novel Covalent Inhibitor Fragment for the SARS-CoV-2 Main Protease Identified by Target-Specific Deep Learning. Acs Chem.Biol. doi:10.1021/acschembio.6c00120
2026 Cooperativity and communication between the active sites of the dimeric SARS-CoV-2 main protease. Sci Adv doi:10.1126/sciadv.aeb0769
2026 Impact of Single Halogen Atom Substitutions on Antiviral Profile of Inhibitors Targeting SARS-CoV‐2 Main Protease. Acs Omega doi:10.1021/acsomega.5c10895
2026 Noncovalent SARS-CoV-2 main protease inhibitors targeting the catalytic dyad and primed substrate binding subsites. Rsc Med Chem doi:10.1039/d6md00401f
2026 From nicotine to SARS-CoV-2 antivirals with potent in vivo efficacy and a broad anti-coronavirus spectrum. Nat Commun doi:10.1038/s41467-026-69527-5
2026 Design, synthesis, and structural characterization of covalent tetrahydroquinoline-based inhibitors of coronavirus 3CLpro. Bioorg.Chem. doi:10.1016/j.bioorg.2026.110402
2026 Discovery of EGT710, an Oral Nonpeptidomimetic Reversible Covalent SARS-CoV-2 Main Protease Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.5c02360
2026 Structure-Based Development of Ultra-Broad-Spectrum 3C-Like Protease Inhibitors. Adv Sci doi:10.1002/advs.202512342
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2026 Investigating the Binding Mode of a Naphthol-Based Inhibitor Targeting SARS-CoV-2 Main Protease. Chemmedchem doi:10.1002/cmdc.70448
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2026 Identification of a Potent Pan-Coronaviral Main Protease Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00645
2026 Fragment-Based Development of NSP14 Exonuclease Inhibitors Confounded by Batch-to-Batch Variability. Acs Chem.Biol. doi:10.1021/acschembio.5c00930
2026 Cleavage at the nsp5-nsp6 site of SARS-CoV-2 main protease intermediate precursor is faster from a monomer than a dimer form. J.Biol.Chem. doi:10.1016/j.jbc.2026.111395
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2026 Crystallographic characterisation and development of bi-substrate inhibitors of coronavirus nsp14 methyltransferase. Rsc Med Chem doi:10.1039/d5md00896d
2026 Deubiquitinase inhibitors: Targeting SARS-CoV-2 papain-like protease with antiviral efficacy in a murine model. Febs J. doi:10.1111/febs.70399
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2026 Structure-Based Design of Covalent SARS-CoV‐2 Main Protease Inhibitors Targeting the Nirmatrelvir-Resistant E166 Mutants. Jacs Au doi:10.1021/jacsau.5c01178
2026 Metal ions govern coronavirus endoribonuclease activity. Nucleic Acids Res. doi:10.1093/nar/gkaf1508
2026 YL1004 is a SARS-CoV-2 papain-like protease inhibitor with immunomodulatory and antiviral activity in mice. Nat Commun doi:10.1038/s41467-026-68795-5
2026 Incorporation of arabinose-CTP and arabinose-UTP inhibits viral polymerases by inducing long pauses. J.Biol.Chem. doi:10.1016/j.jbc.2025.111027
2026 Substrate and target selectivity of 4'-fluoroadenosine against viral and host polymerases. Biorxiv doi:10.64898/2026.05.22.727251
2026 Solution Domain Dynamics of Monomeric SARS-CoV‐2 Main Protease Revealed by Optimized NMR Residual Dipolar Coupling Measurements. ACS Phys Chem Au doi:10.1021/acsphyschemau.5c00081
2025 Accelerating the Hit-To-Lead Optimization of a SARS-CoV-2 Mpro Inhibitor Series by Combining High-Throughput Medicinal Chemistry and Computational Simulations. J.Med.Chem. doi:10.1021/acs.jmedchem.4c02941
2025 Discovery and Preclinical Profile of ALG-097558, a Pan-Coronavirus 3CLpro Inhibitor. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00088