Severe acute respiratory syndrome coronavirus 2 · seed P0DTD1 · 7096 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt P0DTD1 RCSB by accession PDBe-KB AlphaFold DB InterPro CATH 2.40.10.10 CATH 1.10.1840.10 CATH 3.40.50.300 SCOP 8092569 SCOP 8092568 SCOP 8092567 SCOP 8092431 SCOP 8092559 SCOP 8092436 SCOP 8092437 RCSB 9M29 PDBe
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.
Every figure here is counted over the whole family rather than quoted from one entry.
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.
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.
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.
| Entities | Length | Best (Å) | Best entry | What 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.
| Oligomeric state | Chains | Entries | Share |
|---|---|---|---|
| dimeric | 2 | 1,314 | 67.0% |
| monomeric | 1 | 420 | 21.4% |
| hexameric | 6 | 75 | 3.8% |
| tetrameric | 4 | 70 | 3.6% |
| octameric | 8 | 17 | 0.9% |
| trimeric | 3 | 13 | 0.7% |
| pentameric | 5 | 12 | 0.6% |
| nonameric | 9 | 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.
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.
| Domain | Source | Span (seed) | Chains |
|---|---|---|---|
| Trypsin-like serine proteases | CATH 2.40.10.10 | 3274–3354 | 624 |
| main proteinase (3clpro) structure, domain 3 | CATH 1.10.1840.10 | 3464–3564 | 520 |
| P-loop containing nucleotide triphosphate hydrolases | CATH 3.40.50.300 | 5768–5908 | 76 |
| Ubiquitin-like | SCOP2B 8092569 | 1600–1656 | 254 |
| PLpro Zn-binding domain-like | SCOP2B 8092568 | 1773–1836 | 254 |
| Cysteine proteinases | SCOP2B 8092567 | 1803–1872 | 510 |
| Trypsin-like serine proteases | SCOP2B 8092431 | 3264–3453 | 1,234 |
| Nucleotide cyclase/DNA polymerase palm domain-like | SCOP2B 8092559 | 5071–5196 | 144 |
| S-adenosyl-L-methionine-dependent methyltransferases | SCOP2B 8092436 | 6456–6645 | 59 |
| EndoU-like | SCOP2B 8092437 | 6646–6801 | 59 |
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| DMS | cryoprotectant | Dimethyl Sulfoxide | 623 | 1.18 |
| ZN | ion | Zinc Ion | 548 | 1.20 |
| CL | ion | Chloride Ion | 348 | 1.25 |
| PO4 | ion | Phosphate Ion | 175 | 1.42 |
| NA | ion | Sodium Ion | 129 | 1.20 |
| MLI | buffer | Malonate Ion | 107 | 1.65 |
| EDO | cryoprotectant | 1,2-Ethanediol | 95 | 1.20 |
| GOL | cryoprotectant | Glycerol | 94 | 1.31 |
| MG | ion | Magnesium Ion | 71 | 1.47 |
| SO4 | ion | Sulfate Ion | 46 | 1.39 |
| PG4 | cryoprotectant | Tetraethylene Glycol | 39 | 1.31 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 37 | 1.25 |
| 4WI | ligand | (1r,2s,5s)-N-{(1e,2s)-1-Imino-3-[(3s)-2-Oxopyrrolidin-3-Yl]propa | 33 | 1.49 |
| ACT | cryoprotectant | Acetate Ion | 28 | 1.28 |
| IMD | buffer | Imidazole | 20 | 1.40 |
| CIT | buffer | Citric Acid | 18 | 1.64 |
| FMT | buffer | Formic Acid | 14 | 1.28 |
| ADP | cofactor | Adenosine-5'-Diphosphate | 13 | 1.82 |
| 7YY | buffer | 6-[(6-Chloranyl-2-Methyl-Indazol-5-Yl)amino]-3-[(1-Methyl-1,2,4- | 12 | 1.46 |
| K36 | ligand | (1s,2s)-2-({N-[(Benzyloxy)carbonyl]-L-Leucyl}amino)-1-Hydroxy-3- | 11 | 1.35 |
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).
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.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Severe acute respiratory syndrome coronavirus 2 | 1,932 | 1.16 | 1606 | 89% |
| Severe acute respiratory syndrome coronavirus | 13 | 1.50 | 13 | 12% |
| Severe acute respiratory syndrome-related coronavirus | 7 | 2.71 | 2 | 36% |
| SARS-CoV-2 pseudovirus | 3 | 2.18 | 3 | 7% |
| Unknown | 2 | 0 | 17% | |
| Homo sapiens | 1 | 2.05 | 0 | 4% |
| Human betacoronavirus 2c EMC/2012 | 1 | 3.00 | 0 | 8% |
| SARS coronavirus Frankfurt 1 | 1 | 3.38 | 0 | 7% |
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
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.
One record per paper, not per entry.
| Year | Citation |
|---|---|
| 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 |
| 2026 | Optimization of pyridopyrimidinedione derivatives as non-covalent SARS-CoV-2 3CL protease inhibitors. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2026.130619 |
| 2026 | Investigating the Binding Mode of a Naphthol-Based Inhibitor Targeting SARS-CoV-2 Main Protease. Chemmedchem doi:10.1002/cmdc.70448 |
| 2026 | Fragment-Based Design of Targeted Covalent Inhibitors: The Scope and Limitation of Linking Approaches. Chemmedchem doi:10.1002/cmdc.202501108 |
| 2026 | Structural analysis of the flexibility of the Ubl2 domain within the papain-like protease of SARS-CoV-2. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X26003699 |
| 2026 | Next-generation inhibitors of SARS-CoV-2 M pro overcome the deficiencies of Paxlovid. Nat Commun doi:10.1038/s41467-026-71436-6 |
| 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 |
| 2026 | The C117D oxidation mimic reveals the monomeric structure of SARS-CoV-2 main protease. Protein Sci. doi:10.1002/pro.70753 |
| 2026 | Structure-Guided Design of Potent and Selective Covalent Inhibitors Targeting the SARS-CoV-2 Papain-like Protease. J.Med.Chem. doi:10.1021/acs.jmedchem.5c01973 |
| 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 |
| 2026 | Consecutive catalytic steps of viral RNA polymerase and exonuclease suggest a way to overcome intrinsic nucleotide analogue resistance. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2605725123 |
| 2026 | Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals. Nat Commun doi:10.1038/s41467-026-68304-8 |
| 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 |