Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells DOI Creative Commons

В. М. Староверов,

Alexei Galatenko,

E. N. Knyazev

и другие.

PeerJ, Год журнала: 2024, Номер 12, С. e16964 - e16964

Опубликована: Март 27, 2024

Within-host infection dynamics of Omicron dramatically differs from previous variants SARS-CoV-2. However, little is still known about which parameters virus-cell interplay contribute to the observed attenuated replication and pathogenicity Omicron. Mathematical models, often expressed as systems differential equations, are frequently employed study various viruses. Adopting such models for results in vitro experiments can be beneficial a number aspects, model simplification ( e.g ., absence adaptive immune response innate immunity cells), better measurement accuracy, possibility measure additional data types comparison with vivo case. In this study, we consider refinement our previously developed validated based on system integro-differential equations. We fit experimental Delta infections Caco-2 (human intestinal epithelium model) Calu-3 (lung cell lines. The include information initial conditions, infectious virus titers, intracellular viral RNA measurements at several time points post-infection. accurately explains both lines using only three variant- cell-line-specific parameters. Namely, entry rate significantly lower Omicron, triggers stronger cytokine production i.e response) infected cells, ultimately making uninfected cells resistant virus. Notably, differences single parameter rate) insufficient obtain reliable data.

Язык: Английский

COVID-19 drug discovery and treatment options DOI
Jasper Fuk‐Woo Chan, Shuofeng Yuan, Hin Chu

и другие.

Nature Reviews Microbiology, Год журнала: 2024, Номер 22(7), С. 391 - 407

Опубликована: Апрель 15, 2024

Язык: Английский

Процитировано

18
SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids DOI Creative Commons
Romal Stewart, Kexin Yan, Sevannah A. Ellis

и другие.

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 23, 2023

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 and XBB remains controversial. We show that isolates were significantly more pathogenic in K18-hACE2 mice than a isolate, showing increased neurotropic potential, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice, neurons main target infection, neuronal progenitor cells immature infected. results herein suggest evolving may have increasing potential.

Язык: Английский

Процитировано

23
Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies DOI Creative Commons
Niloofar Faraji,

Tahereh Zeinali,

Farahnaz Joukar

и другие.

Heliyon, Год журнала: 2024, Номер 10(9), С. e30208 - e30208

Опубликована: Апрель 25, 2024

The rapid emergence of multiple strains Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has sparked profound concerns regarding the ongoing evolution virus and its potential impact on global health. Classified by World Health Organization (WHO) as variants concern (VOC), these exhibit heightened transmissibility pathogenicity, posing significant challenges to existing vaccine strategies. Despite widespread vaccination efforts, continual SARS-CoV-2 presents a formidable obstacle achieving herd immunity. Of particular is coronavirus spike (S) protein, pivotal viral surface protein crucial for host cell entry infectivity. Mutations within S have been shown enhance confer resistance antibody-mediated neutralization, undermining efficacy traditional platforms. Moreover, undergoes molecular under selective immune pressure, leading diverse with distinct mutation profiles. This review underscores urgent need vigilance adaptation in development efforts combat evolving landscape mutations ensure long-term effectiveness immunization campaigns.

Язык: Английский

Процитировано

11
Current Progress, Challenges and Prospects in the Development of COVID-19 Vaccines DOI
Congrui Zhu,

Shengmei Pang,

Jiaqi Liu

и другие.

Drugs, Год журнала: 2024, Номер 84(4), С. 403 - 423

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

10
Lineage-specific pathogenicity, immune evasion, and virological features of SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3 DOI Creative Commons

Yuanchen Liu,

Xiaoyu Zhao,

Jialu Shi

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 9, 2024

SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated immune resistance of but factors are speculated contribute global dominance, which remain elusive until today. Here, we find that a higher infectivity than in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, demonstrate gained over associates increased entry efficiency conferred by and better cleavage hNECs. Structurally, S455 altered mode binding protein ACE2 at

Язык: Английский

Процитировано

10
Accelerated Adaptation of SARS-CoV-2 Variants in Mice Lacking IFITM3 Preserves Distinct Tropism and Pathogenesis DOI Open Access
Parker Denz,

Jonathan L. Papa,

Matthew I. McFadden

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

ABSTRACT Here we investigated whether interferon induced transmembrane protein 3 (IFITM3), a key antiviral deficient in certain human populations, affects interspecies adaptation of SARS-CoV-2. We found that SARS-CoV-2 Beta and Omicron variants passaged through IFITM3-deficient versus wild type mice exhibit enhanced replication pathogenesis this new host species. Enhancements associated with amino acid substitutions the viral genome, suggesting IFITM3 limits accumulation adaptive mutations. Mouse-adapted viruses enabled comparative studies mice. caused lung dysfunction altered cilia-associated gene programs, consistent broad antigen distribution lungs. Omicron, which shows low pathogenicity upper respiratory tract preference humans, replicated to high nasal titers while showing restrained spatial lungs diminished inflammatory responses compared Beta. Our findings demonstrate deficiency accelerates coronavirus reveal intrinsic variant traits shape tropism, immunity, across hosts. HIGHLIGHTS is critical barrier species strains enable pathology favors nose large airways, leading mild exhibits replication, driving severe inflammation

Язык: Английский

Процитировано

1
Potent and broadly neutralizing antibodies against sarbecoviruses elicited by single ancestral SARS-CoV-2 infection DOI Creative Commons
Lei Yu,

Yajie Wang,

Yuanchen Liu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 7, 2024

Abstract Monoclonal antibody (mAb) therapeutics hold promise for both preventing and treating infectious diseases, especially among vulnerable populations. However, the emergence of various variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges current mAb treatments, emphasizing need more potent broadly neutralizing antibodies. In this study, we employed an unbiased screening approach to discover antibodies successfully isolated two mAbs from individuals with only exposure ancestral SARS-CoV-2. One these antibodies, CYFN1006-1, exhibited robust cross-neutralization against a spectrum SARS-CoV-2 variants, including latest JN.1 KP.2 consistent IC 50 values ranging ∼1 5 ng/mL. Notably, it also displayed broad neutralization activity SARS-CoV related sarbecoviruses, such as WIV1, SHC014, RaTG13, GD-Pangolin. Structural analysis revealed that target shared hotspot but mutation-resistant epitopes, their Fabs locking RBD in “down” conformation through interactions adjacent RBDs, cross-linking Spike trimers into di-trimers block viral infection. vivo studies conducted JN.1-infected hamster model validated protective efficacy its therapeutic potential. These findings suggest that, meticulous approaches, rare activities sarbecoviruses can be identified exclusively virus exposure.

Язык: Английский

Процитировано

5
Effect of metformin in hypothalamic astrocytes from an immunocompromised mice model DOI
Larissa Daniele Bobermin,

Daniele Schauren da Costa,

Aline Daniel Moreira de Moraes

и другие.

Biochimie, Год журнала: 2024, Номер 223, С. 196 - 205

Опубликована: Апрель 18, 2024

Язык: Английский

Процитировано

4
Interferon signaling in the nasal epithelium distinguishes among lethal and common cold coronaviruses and mediates viral clearance DOI Creative Commons
Clayton J. Otter, David M. Renner, Alejandra Fausto

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(21)

Опубликована: Май 17, 2024

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but host viral determinants disease during common cold versus lethal HCoV are poorly understood. We model initial site infection using epithelial cells cultured at an air-liquid interface (ALI). HCoV-229E, HCoV-NL63, human rhinovirus-16 cold-associated that exhibit unique features this model: early antiviral interferon (IFN) signaling, IFN-mediated clearance, preferential replication temperature (33 °C) which confers muted IFN responses. In contrast, SARS-CoV-2 MERS-CoV encode antagonist proteins clearance cultures. Our study identifies shared among viruses, highlighting responses as predictive outcomes nasally directed IFNs potential therapeutics.

Язык: Английский

Процитировано

4
Animal Models for Human-Pathogenic Coronavirus and Animal Coronavirus Research DOI Creative Commons

Fenglian Xiao,

Jincheng Hu,

Minsheng Xu

и другие.

Viruses, Год журнала: 2025, Номер 17(1), С. 100 - 100

Опубликована: Янв. 14, 2025

Coronavirus epidemics have posed a serious threat to both human and animal health. To combat emerging infectious diseases caused by coronaviruses, various infection models been developed applied in research, including non-human primate models, ferret hamster mouse others. Moreover, new approaches utilized develop that are more susceptible infection. These include using viral delivery methods induce the expression of receptors tissues employing gene-editing techniques create genetically modified mice. This has led successful establishment for multiple significantly advancing related research. In contrast, livestock pets can be infected coronaviruses provide valuable insights when used as enabling collection accurate clinical data through analysis post-infection pathological features. However, despite potential insights, there is paucity research pertaining these models. this review, we detailed overview recent progress development cause humans animals suggest ways which adapted further enhance their value

Язык: Английский

Процитировано

0