SARS-COV-2 Variants: Differences and Potential of Immune Evasion

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 18, 2022

The structural spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) plays an essential role in infection and is important target for neutralizing antibody recognition. Mutations the S gene can generate variants concern (VOCs), which improve "viral fitness" through selective or survival advantages, such as increased ACE-2 receptor affinity, infectivity, viral replication, higher transmissibility, resistance to antibodies immune escape, increasing disease severity reinfection risk. Five VOCs have been recognized include B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.617.2 (India), B.1.1.529 (multiple countries). In this review, we addressed following critical points concerning VOCs: a) characteristics SARS-CoV-2 with mutations gene; b) possible evasion from generated vaccination, previous infection, therapies; c) potential risk new pandemic waves induced by worldwide; d) perspectives further studies actions aimed at preventing reducing impact during current COVID-19 pandemic.

Language: Английский

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Proteolytic activation of SARS‐CoV‐2 spike protein

Microbiology and Immunology, Journal Year: 2021, Volume and Issue: 66(1), P. 15 - 23

Published: Sept. 25, 2021

Spike (S) protein cleavage is a crucial step in coronavirus infection. In this review, process discussed, with particular focus on the novel coronavirus, severe acute respiratory syndrome 2 (SARS-CoV-2). Compared influenza virus and paramyxovirus membrane fusion proteins, activation mechanism of S much more complex. The has two sites (S1/S2 S2'), motif for furin protease at S1/S2 site that results from unique four-amino acid insertion one distinguishing features SARS-CoV-2. viral particle incorporates protein, which already undergone by furin, then undergoes further S2' site, mediated type II transmembrane serine (TMPRSS2), after binding to receptor angiotensin-converting enzyme (ACE2) facilitate plasma membrane. addition, SARS-CoV-2 can enter cell endocytosis be proteolytically activated cathepsin L, although not major mode variants enhanced infectivity have been emerging throughout ongoing pandemic, there close relationship between changes cleavability. All four concern carry D614G mutation, indirectly enhances cleavability furin. P681R mutation delta variant directly increases cleavability, enhancing virulence. Changes significantly impact infectivity, tissue tropism, Understanding these mechanisms critical counteracting pandemic.

Language: Английский

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COVID-19 in pregnancy: implications for fetal brain development

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(4), P. 319 - 330

Published: Feb. 14, 2022

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has rarely observed SARS-CoV-2 to date, given potential for profound maternal immune activation (MIA), likely. Here we review evidence that and other viral can result maternal, placental, activation, ultimately offspring morbidity. Finally, highlight need cellular models development better understand short- long-term impacts next generation.

Language: Английский

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Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 15, 2022

Abstract In cultured cells, SARS-CoV-2 infects cells via multiple pathways using different host proteases. Recent studies have shown that the furin and TMPRSS2 (furin/TMPRSS2)-dependent pathway plays a minor role in infection of Omicron variant. Here, we confirm uses furin/TMPRSS2-dependent inefficiently enters mainly cathepsin-dependent endocytosis TMPRSS2-expressing VeroE6/TMPRSS2 Calu-3 cells. This is case despite efficient cleavage spike protein Omicron. However, airways TMPRSS2-knockout mice, significantly reduced. We furthermore show propagation mouse-adapted QHmusX strain human clinical isolates Beta Gamma reduced mice. Therefore, variant isn’t an exception vivo, analysis with mice important when evaluating variants. conclusion, this study shows critically for murine airways, including

Language: Английский

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SARS-CoV-2 and the Host Cell: A Tale of Interactions

Frontiers in Virology, Journal Year: 2022, Volume and Issue: 1

Published: Jan. 12, 2022

The ability of a virus to spread between individuals, its replication capacity and the clinical course infection are macroscopic consequences multifaceted molecular interaction viral components with host cell. heavy impact COVID-19 on world population, economics sanitary systems calls for therapeutic prophylactic solutions that require deep characterization interactions occurring cells. Unveiling how SARS-CoV-2 engages factors throughout life cycle is therefore fundamental understand pathogenic mechanisms underlying design antiviral therapies strategies. Two years into pandemic, this review provides an overview interplay cell, focus machinery compartments pivotal cellular response. Starting cell surface, following replicative through entry pathways, survival in cytoplasm, egress from infected unravels complex network highlighting knowledge has potential set basis development innovative

Language: Английский

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The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

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

Published: Feb. 23, 2022

Abstract The coronavirus disease 2019 (COVID-19) is a highly transmissible caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) that poses major threat to global public health. Although COVID-19 primarily affects system, causing pneumonia and distress in cases, it can also result multiple extrapulmonary complications. pathogenesis of damage patients with probably multifactorial, involving both direct effects SARS-CoV-2 indirect mechanisms associated host inflammatory response. Recognition features complications has clinical implications for identifying progression designing therapeutic strategies. This review provides an overview from immunological pathophysiologic perspectives focuses on potential targets management COVID-19.

Language: Английский

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Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins

Viruses, Journal Year: 2022, Volume and Issue: 14(7), P. 1415 - 1415

Published: June 28, 2022

Molecular mimicry between viral antigens and host proteins can produce cross-reacting antibodies leading to autoimmunity. The coronavirus SARS-CoV-2 causes COVID-19, a disease curiously resulting in varied symptoms outcomes, ranging from asymptomatic fatal. Autoimmunity due molecular may provide an explanation. Thus, we computationally investigated Spike known epitopes. We discovered hotspots highlight two examples with tentative high autoimmune potential implications for understanding COVID-19 complications. show that TQLPP motif thrombopoietin shares similar antibody binding properties. Antibodies induce thrombocytopenia, condition observed patients. Another motif, ELDKY, is shared multiple human proteins, such as PRKG1 involved platelet activation calcium regulation, tropomyosin, which linked cardiac disease. tropomyosin cause complications blood-clotting disorders disease, respectively. Our findings illuminate pathogenesis the importance of considering when developing therapeutic interventions reduce adverse reactions.

Language: Английский

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SARS-CoV-2 Placentitis Associated With B.1.617.2 (Delta) Variant and Fetal Distress or Demise

The Journal of Infectious Diseases, Journal Year: 2022, Volume and Issue: 225(5), P. 754 - 758

Published: Jan. 11, 2022

There is limited information on the specific impact of maternal infection with SARS-CoV-2 B.1.617.2 (delta) variant pregnancy outcomes. We present 2 cases intrauterine fetal demise and 1 case severe distress in setting delta-variant SARS-CoV-2. In all cases, or occurred within 14 days COVID-19 diagnosis. Evaluation revealed viremia, high nasopharyngeal viral load, evidence placental SARS-CoV-2, hallmark features placentitis. suggest that during warrants vigilance for dysfunction compromise regardless disease severity.

Language: Английский

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ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 13, 2022

Despite tremendous progress in the understanding of COVID-19, mechanistic insight into immunological, disease-driving factors remains limited. We generated maVie16, a mouse-adapted SARS-CoV-2, by serial passaging human isolate. In silico modeling revealed how only three Spike mutations maVie16 enhanced interaction with murine ACE2. induced profound pathology BALB/c and C57BL/6 mice, resulting mouse COVID-19 (mCOVID-19) replicated critical aspects disease, including early lymphopenia, pulmonary immune cell infiltration, pneumonia, specific adaptive immunity. Inhibition proinflammatory cytokines IFNγ TNF substantially reduced immunopathology. Importantly, genetic ACE2-deficiency completely prevented mCOVID-19 development. Finally, inhalation therapy recombinant ACE2 fully protected mice from mCOVID-19, revealing novel efficient treatment. Thus, we here present as new tool to model for discovery therapies show that disease severity is determined cytokine-driven immunopathology critically dependent on vivo.

Language: Английский

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The P681H Mutation in the Spike Glycoprotein of the Alpha Variant of SARS-CoV-2 Escapes IFITM Restriction and Is Necessary for Type I Interferon Resistance

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(23)

Published: Nov. 9, 2022

The appearance of new dominant variants concern (VOC) severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to disease 2019 (COVID-19) pandemic. Of these, alpha variant (also known as B.1.1.7), which appeared initially in United Kingdom, became much Europe and North America first half 2021. spike (S) glycoprotein acquired seven mutations two deletions compared ancestral virus, including P681H mutation adjacent polybasic cleavage site, has been suggested enhance S cleavage. Here, we show that protein confers a level resistance beta interferon (IFN-β) human lung epithelial cells. This correlates with an entry restriction mediated by interferon-induced transmembrane (IFITM2) pronounced infection enhancement IFITM3. Furthermore, is essential for IFN-β context-dependent IFITMs S. reduces dependence on endosomal cathepsins, consistent enhanced cell surface entry. However, reversion H681 does not reduce cleaved incorporation into particles, indicating it exerts its effect downstream furin Overall, suggest that, addition adaptive immune escape, associated VOC may well also confer replication and/or transmission advantage through adaptation resist innate mechanisms.

Language: Английский

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