Evidence for an ACE2-Independent Entry Pathway That Can Protect from Neutralization by an Antibody Used for COVID-19 Therapy DOI
Markus Hoffmann, Anzhalika Sidarovich, Prerna Arora

et al.

mBio, Journal Year: 2022, Volume and Issue: 13(3)

Published: April 25, 2022

SARS-CoV-2 variants of concern (VOC) acquired mutations in the spike (S) protein, including E484K, that confer resistance to neutralizing antibodies. However, it is incompletely understood how these impact viral entry into host cells. Here, we analyzed at position 484 have been detected COVID-19 patients cell and antibody-mediated neutralization. We report mutation E484D markedly increased S-driven hepatoma line Huh-7 lung NCI-H1299 without augmenting ACE2 binding. Notably, largely rescued but not Vero from blockade by antibody Imdevimab rendered ACE2-independent. These results suggest naturally occurring allows employ an ACE2-independent mechanism for insensitive against Imdevimab, employed therapy. IMPORTANCE The interaction protein with cellular receptor considered essential infection constitutes key target antibodies induced upon vaccination. using a surrogate system entry, provide evidence can liberate ACE2-dependence may protect virus neutralization used

Language: Английский

ACE2-independent infection of T lymphocytes by SARS-CoV-2 DOI Creative Commons

Xu-Rui Shen,

Rong Geng,

Qian Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 11, 2022

Abstract SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although RNA or antigen has been identified T cells from patients. Here, we confirmed that could detected patient peripheral blood (PBCs) postmortem lung cells, and the infectious virus also antigen-positive PBCs. We next prove infects lymphocytes, preferably activated CD4 + vitro. Upon infection, RNA, subgenomic protein particle can cells. Furthermore, show spike-ACE2/TMPRSS2-independent through using ACE2 knockdown receptor blocking experiments. Next, demonstrate undergone pronounced apoptosis. In vitro cell death likely mitochondria ROS-HIF-1a-dependent pathways. Finally, demonstrated LFA-1, exclusively expresses multiple leukocytes, more entry molecule mediated compared a list other known receptors. Collectively, this work spike-ACE2-independent manner, which shed novel insights into underlying mechanisms SARS-CoV-2-induced COVID-19

Language: Английский

Citations

146
Animal models for COVID-19: advances, gaps and perspectives DOI Creative Commons
Changfa Fan, Yong Wu,

Rui Xiong

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 7, 2022

Abstract COVID-19, caused by SARS-CoV-2, is the most consequential pandemic of this century. Since outbreak in late 2019, animal models have been playing crucial roles aiding rapid development vaccines/drugs for prevention and therapy, as well understanding pathogenesis SARS-CoV-2 infection immune responses hosts. However, current some deficits there an urgent need novel to evaluate virulence variants concerns (VOC), antibody-dependent enhancement (ADE), various comorbidities COVID-19. This review summarizes clinical features COVID-19 different populations, characteristics major including those naturally susceptible animals, such non-human primates, Syrian hamster, ferret, minks, poultry, livestock, mouse sensitized genetically modified, AAV/adenoviral transduced, mouse-adapted strain engraftment human tissues or cells. host receptors proteases essential designing advanced modified models, successful studies on are also reviewed. Several improved alternatives future proposed, reselection alternative receptor genes multiple gene combinations, use transgenic knock-in method, strains establishing next generation mice.

Language: Английский

Citations

84
ACE2-Independent Alternative Receptors for SARS-CoV-2 DOI Creative Commons
Suhyeon Lim, Monica Zhang, Theresa L. Chang

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(11), P. 2535 - 2535

Published: Nov. 16, 2022

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), is highly contagious and remains a major public health challenge despite availability effective vaccines. SARS-CoV-2 enters cells through binding its spike receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (ACE2) receptor in concert with accessory receptors/molecules that facilitate viral attachment, internalization, fusion. Although ACE2 plays critical role replication, expression profiles are not completely associated infection patterns, immune responses, clinical manifestations. Additionally, infects lack ACE2, resistant monoclonal antibodies against RBD vitro, indicating some possess ACE2-independent alternative receptors, which can mediate entry. Here, we discuss these receptors their interactions components for These include CD147, AXL, CD209L/L-SIGN/CLEC4M, CD209/DC-SIGN/CLEC4L, CLEC4G/LSECtin, ASGR1/CLEC4H1, LDLRAD3, TMEM30A, KREMEN1. Most known be involved entry other viruses modulate cellular functions responses. The omicron variant exhibits altered cell tropism an change pathway, emerging variants may use escape pressure ACE2-dependent provided by vaccination RBD. Understanding pathogenesis provide avenues prevention treatment COVID-19.

Language: Английский

Citations

73
A review on evolution of emerging SARS-CoV-2 variants based on spike glycoprotein DOI
Nimisha Ghosh, Suman Nandi, Indrajit Saha

et al.

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 105, P. 108565 - 108565

Published: Jan. 29, 2022

Language: Английский

Citations

61
Omicron SARS-CoV-2 Variant Spike Protein Shows an Increased Affinity to the Human ACE2 Receptor: An In Silico Analysis DOI Creative Commons
Joseph T. Ortega, Beata Jastrzȩbska, Héctor R. Rangel

et al.

Pathogens, Journal Year: 2021, Volume and Issue: 11(1), P. 45 - 45

Published: Dec. 31, 2021

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

Language: Английский

Citations

60
SARS-CoV-2 cell entry beyond the ACE2 receptor DOI Open Access
Shamila D. Alipoor, Mehdi Mirsaeidi

Molecular Biology Reports, Journal Year: 2022, Volume and Issue: 49(11), P. 10715 - 10727

Published: June 26, 2022

Language: Английский

Citations

49
Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages DOI Creative Commons
Katja Hönzke, Benedikt Obermayer,

Christin Mache

et al.

European Respiratory Journal, Journal Year: 2022, Volume and Issue: 60(6), P. 2102725 - 2102725

Published: June 21, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis still elusive.Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied infected human lung explants adult stem cell derived organoids correlate related host factors with tropism, propagation, virulence compared SARS-CoV, influenza Middle East (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used validate ex vivo results.We provide evidence that expression must be considered scarce, thereby limiting propagation alveolus. Instead, lungs COVID-19 samples showed macrophages frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake a inflammatory anti-viral activation, especially "inflammatory macrophages", comparable those induced by SARS-CoV MERS-CoV, but different from NL63 infection.Collectively, our findings indicate severe injury probably results macrophage-triggered rather than viral of compartment.

Language: Английский

Citations

43
Choosing a cellular model to study SARS-CoV-2 DOI Creative Commons
Gabriel Augusto Pires de Souza,

Marion Le Bideau,

Céline Boschi

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: Oct. 21, 2022

As new pathogens emerge, challenges must be faced. This is no different in infectious disease research, where identifying the best tools available laboratories to conduct an investigation can, at least initially, particularly complicated. However, context of emerging virus, such as SARS-CoV-2, which was recently detected China and has become a global threat healthcare systems, developing models infection pathogenesis urgently required. Cell-based approaches are crucial understanding coronavirus biology, growth kinetics, tropism. Usually, laboratory cell lines first line experimental study viral pathogenicity perform assays aimed screening antiviral compounds efficient blocking replication viruses, saving time resources, reducing use animals. determining ideal type can challenging, especially when several researchers have adapt their studies specific requirements. review strives guide scientists who venturing into studying SARS-CoV-2 help them choose right cellular models. It revisits basic concepts virology presents currently

Language: Английский

Citations

43
Hypericin: A natural anthraquinone as promising therapeutic agent DOI
Jingjing Wu, Jia Zhang,

Cong‐Yuan Xia

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 111, P. 154654 - 154654

Published: Jan. 9, 2023

Language: Английский

Citations

31
SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients DOI Creative Commons
Benjamin Charvet, Joanna Brunel,

Justine Pierquin

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(5), P. 106604 - 106604

Published: April 7, 2023

Patients with COVID-19 may develop abnormal inflammatory response, followed in some cases by severe disease and long-lasting syndromes. We show here that vitro exposure to SARS-CoV-2 activates the expression of human endogenous retrovirus (HERV) HERV-W proinflammatory envelope protein (ENV) peripheral blood mononuclear cells from a subset healthy donors, ACE2 receptor infection-independent manner. Plasma and/or sera 221 patients different cohorts, infected successive variants including Omicron, had detectable ENV, which correlated ENV T lymphocytes peaked severity. was also found postmortem tissues lungs, heart, gastrointestinal tract, brain olfactory bulb, nasal mucosa patients. Altogether, these results demonstrate could induce suggest its involvement immunopathogenesis certain COVID-19-associated syndromes thereby relevance development personalized treatment

Language: Английский

Citations

30