Molecule Information

General Information of the Molecule (ID: Mol04328)

• Name: Spike glycoprotein (S) ,Homo sapiens
• Synonyms: E2 ; Peplomer protein
• Molecule Type: Protein
• Gene Name: S
• Gene ID: 43740568
• Sequence:
  MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFS
  NVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLI
  V NNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMD
  LE GKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITR
  FQT LLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPL
  SETK CTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNR
  KRISN CVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQ
  TGKIAD YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIY
  QAGSTPC NGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTN
  LVKNKCVN FNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCS
  FGGVSVITP GTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCL
  IGAEHVNNSY ECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSN
  NSIAIPTNFTI SVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALT
  GIAVEQDKNTQE VFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVT
  LADAGFIKQYGDC LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGW
  TFGAGAALQIPFAM QMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASAL
  GKLQDVVNQNAQALN TLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSL
  QTYVTQQLIRAAEIRA SANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFL
  HVTYVPAQEKNFTTAPA ICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFV
  SGNCDVVIGIVNNTVYDP LQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQK
  EIDRLNEVAKNLNESLIDL QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSC
  CSCLKGCCSCGSCCKFDEDD SEPVLKGVKLHYT
• Function: [Spike protein S1]: Attaches the virion to the cell membraneby interacting with host receptor, initiating the infection. The majorreceptor is host ACE2 . When S2/S2' has been cleaved, binding to the receptortriggers direct fusion at the cell membrane . WhenS2/S2' has not been cleaved, binding to the receptor results ininternalization of the virus by endocytosis using host TFRC and GRM2and leading to fusion of the virion membrane with the host endosomalmembrane . Alternatively, may use NRP1/NRP2 and integrin as entry receptors . Theuse of NRP1/NRP2 receptors may explain the tropism of the virus inhuman olfactory epithelial cells, which express these molecules at highlevels but ACE2 at low levels . The stalk domain of Scontains three hinges, giving the head unexpected orientational freedom. {ECO:0000255|HAMAP-Rule:MF_04099,ECO:0000269|PubMed:32075877, ECO:0000269|PubMed:32142651,ECO:0000269|PubMed:32155444, ECO:0000269|PubMed:32221306,ECO:0000269|PubMed:32817270, ECO:0000269|PubMed:33082293,ECO:0000269|PubMed:33082294, ECO:0000269|PubMed:34903715,ECO:0000269|PubMed:35150743, ECO:0000269|PubMed:36779763,ECO:0000303|PubMed:33082293, ECO:0000305|PubMed:34561887}.; [Spike protein S2]: Precursor of the fusion protein processedin the biosynthesis of the S protein and the formation of virusparticle. Mediates fusion of the virion and cellular membranes byfunctioning as a class I viral fusion protein. Contains two viralfusion peptides that are unmasked after cleavage. The S2/S2' cleavageoccurs during virus entry at the cell membrane by host TMPRSS2 or during endocytosis by host CSTL . In either case, this triggers an extensive andirreversible conformational change leading to fusion of the viralenvelope with the cellular cytoplasmic membrane, releasing viralgenomic RNA into the host cell cytoplasm . Under thecurrent model, the protein has at least three conformational states:pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During fusion of the viral and target cellmembranes, the coiled coil regions adopt a trimer-of-hairpins structure and position the fusion peptide in close proximityto the C-terminal region of the ectodomain. Formation of this structureappears to promote apposition and subsequent fusion of viral and targetcell membranes. {ECO:0000255|HAMAP-Rule:MF_04099,ECO:0000269|PubMed:32703818, ECO:0000269|PubMed:34159616,ECO:0000305|PubMed:34561887}.; [Spike protein S2']: Subunit of the fusion protein that isprocessed upon entry into the host cell. Mediates fusion of the virionand cellular membranes by functioning as a class I viral fusionprotein. Contains a viral fusion peptide that is unmasked after S2cleavage. This cleavage can occur at the cell membrane by host TMPRSS2or during endocytosis by host CSTL .In either case, this triggers an extensive and irreversibleconformational change that leads to fusion of the viral envelope withthe cellular cytoplasmic membrane, releasing viral genomic RNA into thehost cell cytoplasm . Under the current model, theprotein has at least three conformational states: pre-fusion nativestate, pre-hairpin intermediate state, and post-fusion hairpin state.During fusion of the viral and target cell membranes, the coiled coilregions adopt a trimer-of-hairpins structure andposition the fusion peptide in close proximity to the C-terminal regionof the ectodomain. Formation of this structure appears to promoteapposition and subsequent fusion of viral and target cell membranes.{ECO:0000255|HAMAP-Rule:MF_04099, ECO:0000269|PubMed:32703818,ECO:0000269|PubMed:34159616, ECO:0000305|PubMed:34561887}.
• Uniprot ID: SPIKE_SARS2

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Bamlanivimab

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: severe acute respiratory syndrome coronavirus 2 [ICD-11: XN1V8] [1]

• Resistant Disease: severe acute respiratory syndrome coronavirus 2 [ICD-11: XN1V8]
• Resistant Drug: Bamlanivimab
• Molecule Alteration: Mutation; .
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patient-derived allogeneic stem cell transplant model; Homo sapiens
• Mechanism Description: We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.

References

• Ref 1: Failure of bamlanivimab with selection of E484K mutation in an allogeneic stem cell transplant recipient with nosocomial SARS-CoV-2 infection. Antivir Ther. 2024 Feb;29(1):13596535221097495.