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Role of hemagglutinin esterase protein in neurological manifestation of COVID-19
Fluids and Barriers of the CNS volume 18, Article number: 39 (2021)
We read with interest an article by McQuaid et al. , in this article, the authors stated that “The lipid plasma membrane has structural proteins, namely the spike protein (SP), membrane protein, small membrane protein and hemagglutinin-esterase” . For this claim, the authors cited a related study, but there is not any evidence on hemagglutinin-esterase gene in that cited reference . However, according to the scientific evidence the genome of SARS-CoV-2 lacks the hemagglutinin-esterase (HE) gene and it has no HE glycoprotein [3,4,5,6], thus HE has no role in neurological manifestation of COVID-19.
From the emergence of SARS-CoV-2 in December 2019, a great amount of efforts and research have been made to characterize the virus and the clinical course of coronavirus disease 2019 (COVID-19) . SARS-CoV-2 as an enveloped, positive-strand RNA virus is a member of Coronaviridae family in Nidovirales order . According the genetic properties Coronaviridae family is subdivided to 4 genera including: alpha, beta, gamma and deltacoronavirus . In addition, betacoronavirus genus has five subgenera: Embecovirus (lineage A), Sarbecovirus (lineage B), Merbecovirus (lineage C), Nobecovirus (lineage D) and Hibecovirus .
Between human coronaviruses, OC43-CoV and HKU1-CoV are considered as betacoronaviruses of linage A, however, both SARS-CoV and SARS-CoV-2 are betacoronaviruses of linage B and also MERS-CoV is a member of betacoronavirus of C lineage .
Between coronaviruses, betacoronaviruses lineage A including: bovine-CoV, OC43-CoV, HKU1-CoV, mouse hepatitis virus(MHV), harbor HE which acts functionally like spike (S) protein [12, 13]. The gene of HE is transmitted from influenza virus C/D to betacoronavirus lineage A progenitor via horizontal gene as 9-O-Ac-SA–specific hemagglutinin-esterase-fusion (HEF) . The HE in betacoronaviruses lineage A does not show activity of membrane fusion unlike HEF in influenza virus C/D . SARS-CoV-2 as a betacoronavirus of Sarbecovirus subgenus comprises four structural proteins spike (S), envelope (E), membrane protein (M), and nucleoprotein (N) and lacks HE .
In conclusion, HE gene is absent in betacoronaviruses such as SARS-CoV-2, MERS-CoV and SARS-CoV, thus HE has no role in neurological manifestation of COVID-19, however, some betacoronaviruses in subgenera Embecovirus have HE.
Availability of data and materials
- COVID-19 :
Coronavirus Disease 2019
- SARS-CoV :
Severe acute respiratory syndrome-CoV
- SARS-CoV-2 :
Severe acute respiratory syndrome-CoV-2
- MERS-CoV :
Middle East Respiratory Syndrome CoV
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Zandi, M., Karami, H. & Soltani, S. Role of hemagglutinin esterase protein in neurological manifestation of COVID-19. Fluids Barriers CNS 18, 39 (2021). https://doi.org/10.1186/s12987-021-00271-2