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1.
Commun Biol ; 5(1): 1188, 2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2106511

ABSTRACT

SARS-CoV-2 has evolved continuously and accumulated spike mutations with each variant having a different binding for the cellular ACE2 receptor. It is not known whether the interactions between such mutated spikes and ACE2 glycans are conserved among different variant lineages. Here, we focused on three ACE2 glycosylation sites (53, 90 and 322) that are geometrically close to spike binding sites and investigated the effect of their glycosylation pattern on spike affinity. These glycosylation deletions caused distinct site-specific changes in interactions with the spike and acted cooperatively. Of note, the particular interaction profiles were conserved between the SARS-CoV-2 parental virus and the variants of concern (VOCs) Delta and Omicron. Our study provides insights for a better understanding of the importance of ACE2 glycosylation on ACE2/SARS-CoV-2 spike interaction and guidance for further optimization of soluble ACE2 for therapeutic use.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/chemistry , Angiotensin-Converting Enzyme 2/genetics , SARS-CoV-2/genetics , Glycosylation , Peptidyl-Dipeptidase A , Protein Binding
2.
Methods Mol Biol ; 2556: 243-271, 2022.
Article in English | MEDLINE | ID: covidwho-2047965

ABSTRACT

Ongoing seasonal HCoV-OC43 and HCoV-HKU1 (common cold), an ongoing zoonotic infection of highly lethal MERS-CoV in humans (MERS disease), and an ongoing pandemic SARS-CoV-2 (COVID-19) with high mutability giving some variants causing severe illness and death have been reported to attach to sialyl receptors via their spike (S) glycoproteins and via additional short spikes, hemagglutinin-esterase (HE) glycoproteins, for HCoV-OC43 and HCoV-HKU1. There is lack of zoonotic viruses that are origins of HCoV-HKU1 and the first recorded pandemic CoV (SARS-CoV-2) for studies. In this chapter, we review current knowledge of the roles of sialyl glycans in infections with these viruses in distinct infection stages. Determination of the similarities and differences in roles of sialyl glycans in infections with these viruses could lead to a better understanding of the pathogenesis and transmission that is essential for combating infections with CoVs that recognize sialyl glycans.


Subject(s)
COVID-19 , Coronavirus OC43, Human , Middle East Respiratory Syndrome Coronavirus , Esterases , Hemagglutinins , Humans , Polysaccharides , SARS-CoV-2
3.
PLoS Pathog ; 18(6): e1010590, 2022 06.
Article in English | MEDLINE | ID: covidwho-1892333

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been transmitted across all over the world, in contrast to the limited epidemic of genetically- and virologically-related SARS-CoV. However, the molecular basis explaining the difference in the virological characteristics among SARS-CoV-2 and SARS-CoV has been poorly defined. Here we identified that host sialoglycans play a significant role in the efficient spread of SARS-CoV-2 infection, while this was not the case with SARS-CoV. SARS-CoV-2 infection was significantly inhibited by α2-6-linked sialic acid-containing compounds, but not by α2-3 analog, in VeroE6/TMPRSS2 cells. The α2-6-linked compound bound to SARS-CoV-2 spike S1 subunit to competitively inhibit SARS-CoV-2 attachment to cells. Enzymatic removal of cell surface sialic acids impaired the interaction between SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2), and suppressed the efficient spread of SARS-CoV-2 infection over time, in contrast to its least effect on SARS-CoV spread. Our study provides a novel molecular basis of SARS-CoV-2 infection which illustrates the distinctive characteristics from SARS-CoV.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Peptidyl-Dipeptidase A/metabolism , Polysaccharides/metabolism , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
4.
Vaccines (Basel) ; 8(4)2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-969471

ABSTRACT

Among the four genera of influenza viruses (IVs) and the four genera of coronaviruses (CoVs), zoonotic αIV and ßCoV have occasionally caused airborne epidemic outbreaks in humans, who are immunologically naïve, and the outbreaks have resulted in high fatality rates as well as social and economic disruption and losses. The most devasting influenza A virus (IAV) in αIV, pandemic H1N1 in 1918, which caused at least 40 million deaths from about 500 million cases of infection, was the first recorded emergence of IAVs in humans. Usually, a novel human-adapted virus replaces the preexisting human-adapted virus. Interestingly, two IAV subtypes, A/H3N2/1968 and A/H1N1/2009 variants, and two lineages of influenza B viruses (IBV) in ßIV, B/Yamagata and B/Victoria lineage-like viruses, remain seasonally detectable in humans. Both influenza C viruses (ICVs) in γIV and four human CoVs, HCoV-229E and HCoV-NL63 in αCoV and HCoV-OC43 and HCoV-HKU1 in ßCoV, usually cause mild respiratory infections. Much attention has been given to CoVs since the global epidemic outbreaks of ßSARS-CoV in 2002-2004 and ßMERS-CoV from 2012 to present. ßSARS-CoV-2, which is causing the ongoing COVID-19 pandemic that has resulted in 890,392 deaths from about 27 million cases of infection as of 8 September 2020, has provoked worldwide investigations of CoVs. With the aim of developing efficient strategies for controlling virus outbreaks and recurrences of seasonal virus variants, here we overview the structures, diversities, host ranges and host receptors of all IVs and CoVs and critically review current knowledge of receptor binding specificity of spike glycoproteins, which mediates infection, of IVs and of zoonotic, pandemic and seasonal CoVs.

5.
Vaccines ; 8(4):587, 2020.
Article | MDPI | ID: covidwho-815775

ABSTRACT

Among the four genera of influenza viruses (IVs) and the four genera of coronaviruses (CoVs), zoonotic αIV and βCoV have occasionally caused airborne epidemic outbreaks in humans, who are immunologically naïve, and the outbreaks have resulted in high fatality rates as well as social and economic disruption and losses. The most devasting influenza A virus (IAV) in αIV, pandemic H1N1 in 1918, which caused at least 40 million deaths from about 500 million cases of infection, was the first recorded emergence of IAVs in humans. Usually, a novel human-adapted virus replaces the preexisting human-adapted virus. Interestingly, two IAV subtypes, A/H3N2/1968 and A/H1N1/2009 variants, and two lineages of influenza B viruses (IBV) in βIV, B/Yamagata and B/Victoria lineage-like viruses, remain seasonally detectable in humans. Both influenza C viruses (ICVs) in γIV and four human CoVs, HCoV-229E and HCoV-NL63 in αCoV and HCoV-OC43 and HCoV-HKU1 in βCoV, usually cause mild respiratory infections. Much attention has been given to CoVs since the global epidemic outbreaks of βSARS-CoV in 2002–2004 and βMERS-CoV from 2012 to present. βSARS-CoV-2, which is causing the ongoing COVID-19 pandemic that has resulted in 890,392 deaths from about 27 million cases of infection as of 8 September 2020, has provoked worldwide investigations of CoVs. With the aim of developing efficient strategies for controlling virus outbreaks and recurrences of seasonal virus variants, here we overview the structures, diversities, host ranges and host receptors of all IVs and CoVs and critically review current knowledge of receptor binding specificity of spike glycoproteins, which mediates infection, of IVs and of zoonotic, pandemic and seasonal CoVs.

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