Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2

Gu, Yunqing; Cao, Jun; Zhang, Xinyu; Gao, Hai; Wang, Yuyan; Wang, Jia; He, Jinzhi; Jiang, Xiaoyi; Zhang, Jinlan; Shen, Genhai; Yang, Jie; Zheng, Xiangtao; Hu, Gaowei; Zhu, Yuanfei; Du, Shujuan; Zhu, Yangyong; Zhang, Rong; Xu, Jianqing; Lan, Fei; Qu, Di; Xu, Guoliang; Zhao, Yun; Gao, Dong; Xie, Youhua; Luo, Min; Lu, Zhigang

doi:10.1038/s41422-021-00595-6

Cited by 124 publications

(120 citation statements)

References 70 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Together, the results presented in this study indicate that mutations that emerged in the new SARS-CoV-2 Omicron variant enhance the binding affinity of this variant to the host ACE2 receptor, which likely is an important driver of its increased transmissibility. However, it is important to note that SARS-CoV-2 besides ACE2 could also use other cellular receptors as a secondary binding way to target the host cells [19,[41][42][43]. Thus, it cannot be excluded that the changes that emerged in the Omicron viral spike could have an impact on the virus interaction with these secondary cellular receptors, additionally increasing the virus's ability to reach its target.…”

Section: Resultsmentioning

confidence: 99%

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

2021

View full text Add to dashboard Cite

The rise of SARS-CoV-2 variants, with changes that could be related to an increased virus pathogenicity, have received the interest of the scientific and medical community. In this study, we evaluated the changes that occurred in the viral spike of the SARS-CoV-2 Omicron variant and whether these changes modulate the interactions with the angiotensin-converting enzyme 2 (ACE2) host receptor. The mutations associated with the Omicron variant were retrieved from the GISAID and covariants.org databases, and a structural model was built using the SWISS-Model server. The interaction between the spike and the human ACE2 was evaluated using two different docking software, Zdock and Haddock. We found that the binding free energy was lower for the Omicron variant as compared to the WT spike. In addition, the Omicron spike protein showed an increased number of electrostatic interactions with ACE2 than the WT spike, especially the interactions related to charged residues. This study contributes to a better understanding of the changes in the interaction between the Omicron spike and the human host ACE2 receptor.

show abstract

Section: Resultsmentioning

confidence: 99%

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

2021

View full text Add to dashboard Cite

show abstract

“…This type of HERV activation mediated by an interaction between a triggering virus and a specific receptor on certain cells has already been described, e.g., with HHV-6A [33]. Because SARS-CoV-2 induced HERV-W ENV expression in human lymphoid cells that neither express ACE2 nor TMPRSS2 and does not infect them, additional undetermined receptors are expected to mediate HERV activation by SARS-CoV-2, which should now be further studied with recent data on alternative receptors [80].…”

Section: Discussionmentioning

confidence: 84%

SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients

Charvet¹,

Brunel²,

Pierquin³

et al. 2022

Preprint

View full text Add to dashboard Cite

Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.

show abstract

“…It is to be noted that apart from ACE2, recent research [14] has identified cellular proteins like asialoglycoprotein receptor-1 (ASGR1) and Kringle Containing Transmembrane Protein 1 (KREMEN1) as SARS-CoV-2 receptors in Spike glycoprotein. The authors in [14] have shown that both RBD and N-terminal domain bind of Spike glycoprotein bind to ASGR1 and KREMEN1. These two proteins are also believed to affect the viral target cell range as well as antibody-mediated neutralization [16] .…”

Section: Discussionmentioning

confidence: 99%

A review on evolution of emerging SARS-CoV-2 variants based on spike glycoprotein

Ghosh

Nandi

Saha

2022

International Immunopharmacology

View full text Add to dashboard Cite

Since the inception of SARS-CoV-2 in December 2019, many variants have emerged over time. Some of these variants have resulted in transmissibility changes of the virus and may also have impact on diagnosis, therapeutics and even vaccines, thereby raising particular concerns in the scientific community. The variants which have mutations in Spike glycoprotein are the primary focus as it is the main target for neutralising antibodies. SARS-CoV-2 is known to infect human through Spike glycoprotein and uses receptor-binding domain (RBD) to bind to the ACE2 receptor in human. Thus, it is of utmost importance to study these variants and their corresponding mutations. Such 12 different important variants identified so far are B.1.1.7 (Alpha), B.1.351 (Beta), B.1.525 (Eta), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota), B.1.617.1 (Kappa), B.1.617.2 (Delta), C.37 (Lambda), P.1 (Gamma), P.2 (Zeta), P.3 (Theta) and the recently discovered B.1.1.529 (Omicron). These variants have 84 unique mutations in Spike glycoprotein. To analyse such mutations, multiple sequence alignment of 77681 SARS-CoV-2 genomes of 98 countries over the period from January 2020 to July 2021 is performed followed by phylogenetic analysis. Also, characteristics of new emerging variants are elaborately discussed. The individual evolution of these mutation points and the respective variants are visualised and their characteristics are also reported. Moreover, to judge the characteristics of the non-synonymous mutation points (substitutions), their biological functions are evaluated by PolyPhen-2 while protein structural stability is evaluated using I-Mutant 2.0.

show abstract

Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2

Cited by 124 publications

References 70 publications

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis

SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients

A review on evolution of emerging SARS-CoV-2 variants based on spike glycoprotein

Contact Info

Product

Resources

About