Naringenin-7-O-glucoside: Targeting SERPINE1, MMP7, and MMP1 for COVID-19 Lung Pathology and Immune Modulation DOI Creative Commons

Vibha Mishra,

Shivangi Agrawal,

Divya Malik

et al.

Published: Dec. 28, 2023

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been a defining global health crisis, marked severe respiratory distress and high mortality rates. search for effective treatments against this highly mutable virus significant challenge. Here, we explored therapeutic potential of Naringenin-7-O-glucoside (N7G), bioactive flavone glycoside, in context COVID-19. Known its wide-ranging pharmacological effects, including antiviral, antibacterial, antimalarial, anticancer properties, Utilizing gene expression data from EBI Expression Atlas, analyzed lung samples deceased patients healthy individuals to understand N7G’s molecular mechanisms targets. Our enrichment analysis revealed association N7G targets with biological functions pathways crucial immune responses cellular signaling. We highlighted importance such as HIF-1, AGE-RAGE, IL-17 pathogenesis diseases like Suppressing HIF-1 pathway could mitigate inflammation, while targeting AGE-RAGE pathway, key player oxidative stress emerges promising strategy. Modulating implicated cytokine storms during infection, also be effective. Furthermore, relaxin signaling known anti-inflammatory anti-fibrotic was identified target post-COVID-19 syndrome or long-haul COVID. prioritized SERPINE1, MMP7, MMP1 Elevated SERPINE1 levels have linked early risk are involved processes platelet degranulation fibrinolysis impairment, contributing thrombocytopenia. part matrix metalloproteinases family, play roles tissue homeostasis biomarkers COVID-19, pulmonary edema inflammatory responses. docking MD simulation studies, conducted over 200 ns triplicates, demonstrated stable complex formation MMP7 SERPINE1. consistently occupied zinc binding catalytic site similar other inhibitors, tightly bound inhibitor indicating strong interactions. MMGBSA confirmed stability these complexes, suggesting inhibitory Although showed transient MMP1, role pathogenesis, particularly cannot ignored. associated increased patients, underscoring target. In conclusion, our study identifies critical immune-related combating results position novel treating COVID-19-induced inflammation However, initial findings require further validation. This contributes understanding natural compounds viral infection treatment, opening exploring flavonoids viruses. It underscores diverse strategies, substances, challenge

Language: Английский

Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86 DOI Creative Commons
Ninaad Lasrado, Ai‐ris Y. Collier, Nicole P. Hachmann

et al.

Vaccine, Journal Year: 2023, Volume and Issue: 41(47), P. 6904 - 6909

Published: Oct. 21, 2023

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that might evade neutralizing antibodies (NAbs) induced by vaccination or infection. In this study, we show NAb titers are substantially lower to but similar slightly higher than other current circulating variants, including EG.5.1, FL.1.5.1. Moreover, against all these variants were vaccinated individuals a history of XBB.1.5 infection no infection, suggesting potential utility monovalent mRNA boosters.

Language: Английский

Citations

81
Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1 DOI Creative Commons
Yanping Hu, Jing Zou, Chaitanya Kurhade

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: Oct. 12, 2023

The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live neutralization assay compare the evasion ability of BA.2.86 other emerged subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 FL.1.5.1. Our results show that is less evasive than sublineages. EG.5.1, FL.1.5.1 continue significantly induced by parental mRNA vaccine BA.5 Bivalent booster. Notably, when compared more recent descendants, particularly display increased resistance neutralization. Among all tested CH.1.1 exhibits greatest evasion. contrast, XBC.1.6 shows slight reduction but remains comparably sensitive BA.5. Furthermore, XBB.1.5-breakthrough infection enhances breadth potency cross-neutralization. These findings reinforce expectation upcoming would likely boost currently circulating while also underscoring critical importance ongoing surveillance monitor evolution immune variants.

Language: Английский

Citations

46
Recurrent SARS-CoV-2 spike mutations confer growth advantages to select JN.1 sublineages DOI Creative Commons
Qian Wang,

Ian A. Mellis,

Jerren Ho

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 11, 2024

The recently dominant SARS-CoV-2 Omicron JN.1 has evolved into multiple sublineages, with recurrent spike mutations R346 T, F456L, and T572I, some of which exhibit growth advantages, such as KP.2 KP.3. We investigated these in JN.1, examining their individual combined effects on immune evasion, ACE2 receptor affinity, vitro infectivity. F456L increased resistance to neutralization by human sera, including those after breakthrough infections, RBD class-1 monoclonal antibodies, significantly altering antigenicity. T enhanced ACE2-binding affinity modestly boosted the infectivity pseudovirus, without a discernible effect serum neutralization, while T572I slightly bolstered evasion SD1-directed mAbs against JN.1's ancestor, BA.2, possibly SD1 conformation. Importantly, expanding sublineages containing V1104L, showed similar suggesting V1104L does not appreciably affect antibody evasion. Furthermore, hallmark mutation Q493E KP.3 reduced viral infectivity, noticeably impacting neutralization. Our findings illustrate how certain confer advantages population could inform design next COVID-19 vaccine booster.

Language: Английский

Citations

16
Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion DOI Creative Commons
Delphine Planas, Isabelle Staropoli, Vincent Michel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicated IGROV-1 no longer Vero E6 were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhanced NAb against both BA.2.86 displayed affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Language: Английский

Citations

32
Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals ≥12 Years Old: A Phase 2/3 Trial DOI Open Access

Juleen Gayed,

Oyeniyi Diya,

Francine S. Lowry

et al.

Published: Jan. 9, 2024

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of ongoing, open-label, phase 2/3 study monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy, participants ≥12 years old (N=412 [12‒17 years, N=30; 18‒55 N=174; >55 N=208]) who previously received ≥3 doses US-authorized mRNA vaccine, the most recent being BA.4/BA.5-adapted bivalent vaccine ≥150 days before vaccination, were vaccinated. Serum 50% neutralizing titers XBB.1.5, EG.5.1, BA.2.86 measured 7 1 month after vaccination in subset ≥18-year-olds (N=40) positive for SARS-CoV-2 at baseline. Seven-day was also evaluated matched group previous (NCT05472038). There no new signals; local reactions systemic events mostly mild to moderate severity, adverse infrequent, none led withdrawal. The induced numerically higher than robust responses all 3 sublineages month. These support favorable benefit-risk profile 30 μg. NCT05997290

Language: Английский

Citations

10
SARS-CoV-2 BA.2.86 (“Pirola”): Is it Pi or Just Another Omicron Sublineage? DOI Creative Commons
Daniele Focosi, Pietro Giorgio Spezia, Fabrizio Maggi

et al.

Vaccines, Journal Year: 2023, Volume and Issue: 11(11), P. 1634 - 1634

Published: Oct. 25, 2023

The SARS-CoV-2 sublineage BA [...].

Language: Английский

Citations

14
The wind of change: Gibbs energy of binding and infectivity evolution of Omicron BA.2.86 Pirola, EG.5.1, XBB.1.16 Arcturus, CH.1.1 and BN.1 variants of SARS-CoV-2 DOI
Marko Popovic, Gavrilo Šekularac, Marta Popović

et al.

Microbial Risk Analysis, Journal Year: 2024, Volume and Issue: 26, P. 100290 - 100290

Published: Feb. 1, 2024

Language: Английский

Citations

4
Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine DOI Open Access

Chaoyue Zhao,

Guonan Cai,

Shuai Jiang

et al.

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: June 23, 2024

In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses notable resistance to conventional treatments due their rapid evolution emergence diverse variants, particularly within SARS-CoV-2. This study investigates development broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through ‘Knob-into-Hole’ technique. We constructed various recombinant incorporating receptor-binding domains (RBDs) different coronaviruses. Heterodimers combining RBDs from with those SARS-CoV or MERS-CoV elicited superior neutralizing responses compared homodimeric in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD MERS_D614G/BA.1_XBB.1.5-RBD, demonstrated remarkable breadth potency all known related sarbecoviruses like GD-Pangolin WIV1, even pseudoviruses. Furthermore, these also enhanced cellular immune responses. These findings underscore potential hetero a universal vaccine strategy against current future threats.

Language: Английский

Citations

0
Naringenin-7-O-glucoside: Targeting SERPINE1, MMP7, and MMP1 for COVID-19 Lung Pathology and Immune Modulation DOI Creative Commons

Vibha Mishra,

Shivangi Agrawal,

Divya Malik

et al.

Published: Dec. 28, 2023

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been a defining global health crisis, marked severe respiratory distress and high mortality rates. search for effective treatments against this highly mutable virus significant challenge. Here, we explored therapeutic potential of Naringenin-7-O-glucoside (N7G), bioactive flavone glycoside, in context COVID-19. Known its wide-ranging pharmacological effects, including antiviral, antibacterial, antimalarial, anticancer properties, Utilizing gene expression data from EBI Expression Atlas, analyzed lung samples deceased patients healthy individuals to understand N7G’s molecular mechanisms targets. Our enrichment analysis revealed association N7G targets with biological functions pathways crucial immune responses cellular signaling. We highlighted importance such as HIF-1, AGE-RAGE, IL-17 pathogenesis diseases like Suppressing HIF-1 pathway could mitigate inflammation, while targeting AGE-RAGE pathway, key player oxidative stress emerges promising strategy. Modulating implicated cytokine storms during infection, also be effective. Furthermore, relaxin signaling known anti-inflammatory anti-fibrotic was identified target post-COVID-19 syndrome or long-haul COVID. prioritized SERPINE1, MMP7, MMP1 Elevated SERPINE1 levels have linked early risk are involved processes platelet degranulation fibrinolysis impairment, contributing thrombocytopenia. part matrix metalloproteinases family, play roles tissue homeostasis biomarkers COVID-19, pulmonary edema inflammatory responses. docking MD simulation studies, conducted over 200 ns triplicates, demonstrated stable complex formation MMP7 SERPINE1. consistently occupied zinc binding catalytic site similar other inhibitors, tightly bound inhibitor indicating strong interactions. MMGBSA confirmed stability these complexes, suggesting inhibitory Although showed transient MMP1, role pathogenesis, particularly cannot ignored. associated increased patients, underscoring target. In conclusion, our study identifies critical immune-related combating results position novel treating COVID-19-induced inflammation However, initial findings require further validation. This contributes understanding natural compounds viral infection treatment, opening exploring flavonoids viruses. It underscores diverse strategies, substances, challenge

Language: Английский

Citations

1