12  Covid-19 and autoimmunity: The role of molecular mimicry
Notwithstanding the current wave of intensive worldwide research, the ethiopathology of the diseases induced by the SARS-CoV-2 infection is the central question that remains obscure. One likely explanation is that the heterogeneity and multitude of the disorders induced by the current pandemic derive from molecular mimicry phenomena between the virus and human proteins. The scientific rationale is that, following the infection, the immune responses raised against SARS-CoV-2 may cross-react with human proteins that share peptide sequences with the virus, in this way leading to autoimmune pathologic sequelae [120]. Actually, a recent report [121] militates in this direction and likely explains lungs and airways dysfunctions through the sharing of peptides between SARS-CoV-2 glycoprotein and alveolar lung surfactant proteins [121]. Moreover, in the clinical context exposed above, it is of note to report that Sars.CoV-2 shares 6 minimal immune determinants (KTVLK, TPEEH, RETMS, PFVVS, GLEAP, ICLLQ) with the Kawasaki antigen Inositol-trisphosphate 3-kinase C [122], thus highlighting as likely cross-reactions and consequent autoimmune Kawasaki disease in predisposed subjects. Even more impressing it appears the heptapeptide sharing between the human proteome and the viral spike glycoprotein shown in Table 1 . The clinical scenario that emerges is upsetting. Indeed, the list of proteins reported in the table – when altered – configurate almost all the diseases that have been described in association with SARS-CoV-2. Two examples from the table are 1) Histone-lysine N-methyltransferase 2C that may associate with neurodevelopmental disorders., seizures, behavioral abnormalities [123], and 2) Interleukin-7 that plays a central, critical role in the regulation of the immune system and associates with severe lymphopenia when deficient [124].
Table 1 Heptapeptide sharing between SARS-CoV-2 spike glycoprotein and the human proteins.
Peptide Human Protein Name
SSTASAL 40S ribosomal protein S13
KLNDLCF Interleukin-7
FLPFFSN OTU domain-containing protein 6A
EIDRLNE Protein SET
IGAGICA Hepatitis A virus cellular receptor 2
EIDRLNE Protein SETSIP
LDKYFKN Follistatin-related protein 1
VSGTNGT Lysosome-associated membrane glycoprotein 1
FKNLREF Isovaleryl-CoA dehydrogenase, mitochondrial
LPPLLTD Maestro heat-like repeat-containing protein family member 9
DKVFRSS Zinc finger protein 528
LVKQLSS E3 SUMO-protein ligase PIAS1
VTLADAG Non-receptor tyrosine-protein kinase TNK1
RRARSVAS Amiloride-sensitive sodium channel subunit alpha
SPRRARS Hermansky-Pudlak syndrome 1 protein
KVEAEVQ EMILIN-3
TRFQTLL Disheveled-associated activator of morphogenesis 2
VYSTGSN Neural cell adhesion molecule L1-like protein
GLTVLPP FH1/FH2 domain-containing protein 3
SLLIVNN ATP-binding cassette sub-family A member 10
DEDDSEPV Unconventional myosin-XVI
NASVVNI Thyroid adenoma-associated protein
LIRAAEI Unconventional myosin-XVIIIa
TGRLQSL Neuron navigator 3
DEVRQIA Histone-lysine N-methyltransferase 2C
SSSGWTA Transmembrane protein KIAA1109
Data on protein function/disease from Uniprot (https://www.uniprot.org/).
Sequential overlapping heptapeptides are given bold.