Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance DOI Creative Commons
Clayton J. Otter, David M. Renner, Alejandra Fausto

et al.

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

Published: Dec. 19, 2023

SUMMARY 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 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.

Language: Английский

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

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(21)

Published: May 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.

Language: Английский

Citations

5
Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses DOI Creative Commons
Shella Gilbert-Girard, Jocelyne Piret, Julie Carbonneau

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(7), P. e1012017 - e1012017

Published: July 22, 2024

Some respiratory viruses can cause a viral interference through the activation of interferon (IFN) pathway that reduces replication another virus. Epidemiological studies coinfections between SARS-CoV-2 and other have been hampered by non-pharmacological measures applied to mitigate spread during COVID-19 pandemic. With ease these interventions, influenza A now co-circulate. It is thus prime importance characterize their interactions. In this work, we investigated effects an Omicron variant contemporary A/H3N2 strain, in comparison with ancestral strain 2009 pandemic A/H1N1 We infected nasal human airway epitheliums influenza, either simultaneously or 24 h apart. Viral load was measured RT-qPCR IFN-α/β/λ1/λ2 proteins were quantified immunoassay. Expression four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) also RT-droplet digital PCR. Additionally, susceptibility each virus IFN-α/β/λ2 recombinant determined. Our results showed A, especially A/H3N2, interfered both viruses, but did not significantly interfere A/H1N1. Consistently results, particularly caused higher production IFN expression ISGs than SARS-CoV-2. induced marginal reduced response influenza. All susceptible exogenous IFNs, being less type I III respectively. Thus, causes towards most likely response. The opposite necessarily true, concurrent infection leads lower Taken together, help us understand how interacts major pathogen.

Language: Английский

Citations

4
Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition DOI Creative Commons
Muzaffar Kayumov, Parthiban Marimuthu, Jamoliddin Razzokov

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 4, 2025

The emergence of the SARS-CoV-2 virus caused COVID-19 outbreak leading to a global pandemic. Natural substances started being screened for their antiviral activity by computational and in-vitro techniques. Here, we evaluated anti-SARS-CoV-2 main protease (M pro ) efficacy © Rutan, which contains five polyphenols (R5, R6, R7, R7’, R8) extracted from sumac Rhus coriaria L. We obtained three fractions after large-scale purification: fraction 1 held R5, 2 consisted R7 3 R8. In vitro results showed anti-M potential: IC 50 values R5 R8 made 42.52 µM 5.48 µM, respectively. Further, studied M -polyphenol interactions in silico analysis understand mechanistic extrapolation Rutan binding nature with . extensively incorporated series Initially, docking protocol validation, redocking co-crystal ligand GC-376* pocket was carried out. representative docked complexes were subjected long-range 500 ns molecular dynamics simulations. free energy (BFE kcal/mol) components calculated as follows: (−104.636) > R6 (−93.754) R7’ (−92.113) (−81.115) (−67.243). correspond outcomes. Furthermore, per-residue decomposition C145, E166, Q189 residues hotspot contributing maximum BFE energies. All effectively interact catalytic form stable that allow estimation inhibitory activity. Assay kit analyses revealed its have effective

Language: Английский

Citations

0
Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning DOI Creative Commons
Teena Bajaj, Babak Mosavati, Lydia H. Zhang

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(13), P. 10243 - 10256

Published: Jan. 1, 2025

This study presented a novel screening of acrylamides discovering them as inhibitors against Nsp15 from SARS-CoV-2 and utilizing the data to develop an AI model screen more virtually.

Language: Английский

Citations

0
Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses DOI Creative Commons
Shella Gilbert-Girard, Jocelyne Piret, Julie Carbonneau

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 3, 2024

Abstract Some respiratory viruses can cause a viral interference through the activation of interferon (IFN) pathway that reduces replication another virus. Epidemiological studies coinfections between SARS-CoV-2 and other have been hampered by non-pharmaceutical measures applied to mitigate spread during COVID-19 pandemic. With ease these interventions, influenza A now co-circulate. It is thus prime importance characterize their interactions. In this work, we investigated effects an Omicron variant contemporary A/H3N2 strain, in comparison with ancestral strain 2009 pandemic A/H1N1 We infected nasal human airway epitheliums influenza, either simultaneously or 24 h apart. Viral load was measured RT-qPCR IFN-α/β/λ1/λ2 proteins were quantified immunoassay. Expression four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) also RT-droplet digital PCR. Additionally, susceptibility each virus IFN-α/β/λ2 recombinant determined. Our results showed A, especially A/H3N2, interfered both viruses, but only A/H1N1. Consistently results, particularly caused higher production IFN expression ISGs than SARS-CoV-2. The induced marginal its presence associated reduced response. All susceptible exogenous IFNs, being less type I III respectively. Thus, causes towards most likely opposite not necessarily true, concurrent infection leads lower Taken together, help us understand how interacts major pathogen. Author summary During pandemic, able reduce viruses. Since measures, variants such as started co-circulate infect same host interact other. These interactions lead attenuated aggravated infections affect timing epidemics. Therefore, it very important elucidate new better predict implications health epidemic activity. work contributes using co-circulated after lifting mitigation i.e., strain. studied may virus’ growth innate immune response host. found prior decrease while latter interplay improve mathematical models predicting

Language: Английский

Citations

3
Exploration of isatin-based inhibitors of SARS-CoV-2 Nsp15 endoribonuclease DOI
Θεόδωρος Ράμπιας,

Thomas Antoniou,

Annelies Stevaert

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 279, P. 116886 - 116886

Published: Sept. 16, 2024

Language: Английский

Citations

1
SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness DOI Creative Commons
Yiyang Zhou,

Yani P. Ahearn,

Kumari G. Lokugamage

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Coronaviruses (CoVs) maintain large RNA genomes that frequently undergoes mutations and recombination, contributing to their evolution emergence. In this study, we find SARS-CoV-2 has greater recombination frequency than other human CoVs. addition, coronavirus primarily occurs at uridine (U)-enriched sequences. Therefore, next evaluated the role of NSP15, a viral endonuclease targets uridines (EndoU), in virus infection. Using catalytically inactivated EndoU mutant (NSP15

Language: Английский

Citations

1
Dimming the corona: studying SARS-coronavirus-2 at reduced biocontainment level using replicons and virus-like particles DOI Creative Commons
Grace Neilsen,

Asha Maria Mathew,

J.M. Castro

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

The coronavirus-induced disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, has had a devastating impact on millions of lives globally, with mortality rates and catastrophic social implications. Developing tools for effective vaccine strategies platforms is essential controlling preventing the recurrence such pandemics. Moreover, molecular virology that facilitate study viral pathogens, mutations, interactions various host proteins are essential. Viral replicon- virus-like particle (VLP)-based systems excellent examples tools. This review outlines importance, advantages, disadvantages both VLP-based have been developed SARS-CoV-2 helped scientific community in dimming intensity COVID-19 pandemic.

Language: Английский

Citations

0
SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity DOI Open Access
Xionglue Wang, Bin Zhu

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

Published: Dec. 12, 2023

SUMMARY It has been proposed that coronavirus nsp15 mediates evasion of host cell double-stranded (ds) RNA sensors via its uracil-specific endoribonuclease activity. However, how processes viral dsRNA, commonly considered as a genome replication intermediate, remains elusive. Previous research mainly focused on short single-stranded substrates, and whether prefers or for cleavage is controversial. In the present work, we prepared numerous including both long substrates mimicking defined RNA, to clarify substrate preference pattern SARS-CoV-2 nsp15. We demonstrated preferentially cleaved flexible pyrimidine nucleotides located in AU-rich areas mismatch-containing dsRNA nicking manner. The AU content distribution along with length affected by Because genomes generally have high content, our work supported mechanism coronaviruses evade antiviral response mediated using nickase directly cleave intermediates formed during transcription.

Language: Английский

Citations

0
Interferon signaling in the nasal epithelium distinguishes among lethal and common cold respiratory viruses and is critical for viral clearance DOI Creative Commons
Clayton J. Otter, David M. Renner, Alejandra Fausto

et al.

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

Published: Dec. 19, 2023

SUMMARY 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 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.

Language: Английский

Citations

0