The puzzling mutational landscape of the SARS‐2‐variant Omicron

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(5), P. 2019 - 2025

Published: Jan. 8, 2022

The recently emerging SARS-CoV-2 variant omicron displays an unusual association of 30 mutations, 3 deletions, and 1 insertion. To analyze the impact this atypic mutational landscape, we constructed a complete structure spike protein. Compared with delta variant, receptor-binding domain (RBD) has increased electrostatic surface potential, but decreased affinity for ACE-2 receptor. N-terminal (NTD) both potential lower lipid rafts. is predicted to be less fusogenic thus pathogenic than delta, due geometric reorganization S1-S2 cleavage site. Overall, these virological parameters suggest that does not have significant infectivity advantage over variant. However, in omicron, neutralizing epitopes are greatly affected, suggesting current vaccines will probably confer little protection against In conclusion, puzzling pattern combines contradictory properties which may either decrease (virological properties) or increase (immunological escape/facilitation) transmission human population. This Janus-like phenotype explain some conflicting reports on initial assessment provide new insights about molecular mechanisms controlling its dissemination pathogenesis worldwide.

Language: Английский

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Twin combination of Omicron and Delta variants triggering a tsunami wave of ever high surges in COVID‐19 cases: A challenging global threat with a special focus on the Indian subcontinent

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(5), P. 1761 - 1765

Published: Jan. 11, 2022

The emergence of Omicron (B.1.1.529) variant SARS-CoV-2 has resulted into a very massive surge in COVID-19 cases worldwide. Due to continuous multiple variants SARS-CoV-2, the ongoing pandemic caused severe morbidity and mortality last two years. rate infectivity is much higher than Delta quick time displaced now become dominant across globe. twin combination triggering Tsunami wave ever high surges This article highlights global threats challenges posed by Omicron, strategies counter it with particular focus on Indian sub-continent.

Language: Английский

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YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD‐L1/VEGFA Axis

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 21, 2024

Abstract N6‐methyladenosine (m 6 A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion angiogenesis are characteristic features of its TME. The role YTH RNA binding protein 2 (YTHDF2), as an m A reader, in regulating HCC TME not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 27 acetylation promoter region YTHDF2 enhanced expression HCC, upregulated predicted a worse prognosis. Animal experiments demonstrated Ythdf2 depletion inhibited spontaneous formation, while overexpression promoted xenografted progression. Mechanistically, recognized 5′‐untranslational ETS variant transcription factor 5 (ETV5) mRNA recruited eukaryotic translation initiation 3 subunit B to facilitate translation. Elevated ETV5 induced programmed death ligand‐1 vascular endothelial growth A, thereby promoting angiogenesis. Targeting via small interference RNA‐containing aptamer/liposomes successfully both Together, this findings reveal potential application prognosis targeted treatment.

Language: Английский

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Mutational and phylogenetic analyses of the two lineages of the Omicron variant

Journal of Medical Virology, Journal Year: 2021, Volume and Issue: 94(5), P. 1777 - 1779

Published: Dec. 29, 2021

Based on the recommendation of WHO's Technical Advisory Group Virus Evolution, WHO designated variant B.1.1.529 as a concern (VOC) and named Omicron 26 November, 2021. was first observed in Africa mid-November 2021.1 The infection by this has been rapidly spreading 85 countries have already reported cases human with 15 December 2021.2 rapid spread again fueled fears COVID-19 all around world like other four VOCs (Alpha, Beta, Gamma, Delta). Recently, classified into two different lineages BA.1 BA.2 based mutations, some which are common unique to both lineages.3, 4 Still, there is no clear evidence or published article mutational diversity phylogenetic analysis these lineages. Therefore, present study, we performed whole-genome mapping We downloaded 6 genome sequences each BA.2, also sequence prototype strain (hCoV-19/Wuhan/WIV04/2019) from Global Initiative Sharing All Influenza Data (GISAID) according protocol described Sarkar et al.5, Each six genomes found 51 mutations dispersed throughout genome, 32 lineages, whereas lineage 19 signature mutations. Among 21 S glycoprotein rest 11 coding regions (ORF1ab, E, M, N). Nineteen include 13 that includes 7 (Table 1). Phylogenetic 12 variant, encompassing along 2000 25 clades Ultrafast Sample placement Existing tRees,6, revealed formed new cluster emerged 20B clade (also known GR) subdivided subclusters (BA.1 BA.2) (Figure mediates virus attachment ACE2 receptor, membrane fusion, entry host cell, acts primary target for neutralizing antibodies elicited immune response.8 Presence 34 28 respectively, raising whether increased transmissibility, escape potential, virulence compared circulating SARS-CoV-2 strains especially Delta currently dominating worldwide. Seven (G142D, K417N, T478K, N501Y, D614G, H655Y, P681H) three (∆HV69del, T95I, ∆YY144del) overlap Delta) previously linked high viral binding affinity, evasion.9-12 Functional implication remaining still unknown, leaving question how whole set will affect fitness. Preliminary indicated infectivity transmission rate Delta.13-15 However, population immunity due transmissibility and/or evasion remains unclear. Though, recent studies claimed properties Omicron.14-17 existing evidence, anticipated overtake areas where community occurs. severity elusive. South suggested may be less severe than Delta,18 patients, infected Omicron, EU EEA either showed mild symptoms were asymptomatic.19 Detection accuracy routinely used PCR antigen-based diagnostic test (Ag-RDT) assays not influenced most strains. gene failure (SGTF) RT-PCR assay multiple deletions NTD glycoprotein, skip SGTF lack NTD. Overall, global threat related very its potential humoral response lead another wave consequences.19 authors acknowledge University Grants Commission (UGC) India providing fellowship Swagata Majumdar. would GISAID (https://www.gisaid.org/) facilitating open data sharing. declare conflict interests. Majumdar Rakesh conceived study. retrieval analysis. drafted manuscript. revised manuscript approved final submission. support findings study available corresponding author upon reasonable request.

Language: Английский

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The Importance of Vaccination in the Context of the COVID-19 Pandemic: A Brief Update Regarding the Use of Vaccines

Vaccines, Journal Year: 2022, Volume and Issue: 10(4), P. 591 - 591

Published: April 12, 2022

The COVID-19 pandemic has led the world to undertake largest vaccination campaign in human history. In record time, unprecedented scientific and governmental efforts have resulted acquisition of immunizers utilizing different technologies (nucleotide acids, viral vectors, inactivated protein-based vaccines). Currently, 33 vaccines already been approved by regulatory agencies countries, more than 10 billion doses administered worldwide. Despite undeniable impact on control pandemic, recurrent emergence new variants interest raised challenges. recent mutations precede outbreaks that rapidly spread at global proportions. addition, reducing protective efficacy rates observed among main authorized vaccines. Besides these issues, several other crucial issues for appropriate combatting remain uncertain or under investigation. Particularly noteworthy include use vaccine-boosting strategies increase protection; concerns related long-term safety vaccines, child immunization reliability uncommon adverse events; persistence virus society; transition from a an endemic state. this review, we describe updated scenario regarding SARS-CoV-2 outline current discussions covering vaccine efficacy, future perspectives.

Language: Английский

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Nasally delivered interferon-λ protects mice against infection by SARS-CoV-2 variants including Omicron

Cell Reports, Journal Year: 2022, Volume and Issue: 39(6), P. 110799 - 110799

Published: April 21, 2022

Although vaccines and monoclonal antibody countermeasures have reduced the morbidity mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, variants constellations of mutations in spike gene jeopardize their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution needed. The host-derived cytokine interferon lambda (IFN-λ) has been proposed as a possible treatment based on studies human 2019 (COVID-19) patients. Here, we show IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) B.1.1.529 (Omicron) three strains conventional ACE2 transgenic mice. Prophylaxis or therapy nasally delivered IFN-λ2 limits infection historical variant upper lower tracts without causing excessive inflammation. In lung, is produced preferentially epithelial cells acts radio-resistant protect infection. Thus, inhaled may promise for evolving develop resistance antibody-based countermeasures.

Language: Английский

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Binding of human ACE2 and RBD of Omicron enhanced by unique interaction patterns among SARS‐CoV‐2 variants of concern

Journal of Computational Chemistry, Journal Year: 2022, Volume and Issue: 44(4), P. 594 - 601

Published: Nov. 18, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, has continued to mutate and spread worldwide despite global vaccination efforts. In particular, Omicron variant, first identified in South Africa late November 2021, become dominant strain worldwide. Compared original Wuhan, features 50 genetic mutations, with 15 mutations receptor-binding domain (RBD) of spike protein, which binds human angiotensin-converting enzyme (ACE2) receptor for viral entry. However, it is not completely understood how these alter interaction binding strength between RBD ACE2. this study, we used a combined steered molecular dynamics (SMD) simulation experimental microscale thermophoresis (MST) approach quantify We report that brings an enhanced RBD-ACE2 interface through N501Y, Q498R, T478K mutations; changes further lead unique patterns, reminiscing previously dominated variants, Alpha (N501Y) Delta (L452R T478K). Among Q493K Q493R, Q493R shows stronger ACE2 than due increased interactions. Our MST data confirmed are associated five-fold higher affinity compared strain. conclusion, our results could help explain variant's prevalence populations, as forces or likely promote greater internalization, leading infectivity.

Language: Английский

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Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

GeroScience, Journal Year: 2022, Volume and Issue: 44(2), P. 619 - 637

Published: March 8, 2022

Language: Английский

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Reduction in the infection fatality rate of Omicron variant compared with previous variants in South Africa

International Journal of Infectious Diseases, Journal Year: 2022, Volume and Issue: 120, P. 146 - 149

Published: April 21, 2022

The SARS-CoV-2 Omicron (B.1.1.529) variant has caused global concern. Previous studies have shown that the enhanced immune evasion ability and transmissibility reduced severity.In this study, we developed a mathematical model with time-varying transmission rate, vaccination, evasion. We fit to reported case death data up February 6, 2022 estimate infection fatality ratio of in South Africa.We found high relative was mainly due its ability, whereas rate substantially decreased by approximately 78.7% (95% confidence interval: 66.9%, 85.0%) respect previous variants.On basis from Africa modeling, is highly transmissible but significantly lower rates than those variants SARS-CoV-2.

Language: Английский

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Understanding the omicron variant (B.1.1.529) of SARS-CoV-2: Mutational impacts, concerns, and the possible solutions

Annals of Medicine and Surgery, Journal Year: 2022, Volume and Issue: 78

Published: May 7, 2022

Despite many nations' best efforts to contain the so-called COVID-19 pandemic, emergence of SARS-CoV-2 Omicron strain (B.1.1.529) has been identified as a serious concern. After more than two years pandemic and year worldwide vaccination efforts, globe will not be free variants such Delta variants. According current statistics, variant 30 mutations when contrasted other VOCs Alpha (B.1.1.7), Beta (B.1.351), (B.1.617.2). High numbers changes, particularly in spike protein (S-Protein), raise worries about virus's capacity resist pre-existing immunity acquired by or spontaneous infection antibody-based therapy. The raised international concerns, resuming travel bans coming up with questions its severity, transmissibility, testing, detection, vaccines efficiency against it. Additionally, inadequate health care infrastructures immunocompromised individuals increase susceptibility. status low rates play significant role omicron spreading create fertile ground for producing new As result, this article emphasizes mutational changes their consequences. In addition, potential preventing measures have examined detail.

Language: Английский

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