Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
PPIs
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All N‑acetylcysteine studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19early.org COVID-19 treatment researchN-acetylcysteineN-acetylcys.. (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern

Frasson et al., Journal of Molecular Cell Biology. doi:10.1093/jmcb/mjae004
Feb 2024  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
14th treatment shown to reduce risk in February 2021
 
*, now with p = 0.000028 from 24 studies, recognized in 3 countries.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 98 treatments. c19early.org
In Vitro study showing that inhibition of host cell factors rather than viral elements may prevent emergence of SARS-CoV-2 variants resistant to current drugs. Authors identified host genes/proteins commonly required for infection by major variants using CRISPR screening of infected human lung cells. Targeting hits RIPK4, SLC7A11 or MASTL with existing drugs blocked variant replication and virus-induced cytotoxicity. Mechanistic studies revealed variants rapidly induce reactive oxygen species (ROS), while ROS suppression with antioxidants (NAC/GSH) potently blocked infection. NAC treatment in infected humanized mice reduced lung viral load.
9 preclinical studies support the efficacy of N-acetylcysteine for COVID-19:
NAC may be beneficial for COVID-19 by replenishing glutathione stores and reinforcing the glutathione peroxidase-4 pathway to inhibit ferroptosis, an oxidative stress-induced cell death pathway implicated in COVID-199. N-acetylcysteine shows dose-dependent inhibition of SARS-CoV-23,6,8, shows anti-inflammatory and immunomodulatory effects against SARS-CoV-2-induced immune responses in combination with bromelain5, suppressed virus-induced reactive oxygen species and blocked viral replication in a humanized mouse model and in human lung cells4, and may limit COVID-19 induced cardiac damage by boosting cellular antioxidant defenses and potentially mitigating the oxidative stress caused by spike protein-induced ROS production in cardiac fibroblasts10.
Frasson et al., 1 Feb 2024, peer-reviewed, 16 authors.
This PaperN-acetylcys..All
Abstract: Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern A N U SC RI PT 1 Department of Molecular Medicine, University of Padua, Padua 35121, Italy 2 Department of Biology, Armenise/Harvard Pluripotent Stem Cell Biology Laboratory, University of Padua, Padua 35131, Italy 3 Department. of Surgery, Oncology and Gastroenterology, University of Padua, Padua 35128, Italy 4 Veneto Institute of Oncology IOV-IRCCS, Padua 35128, Italy 5 Department of Comparative Biomedicine and Food Science, University of Padua, Padua 35020, Italy 6 Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli 80078, Italy 7 Department of Translational Medicine, Federico II University, Naples 80138, Italy 8 School for Advanced Studies, Genomics and Experimental Medicine Program, University of Naples “Federico II”, Naples 80138, Italy 9 Microbiology and Virology Unit, Padua University Hospital, Padua 35128, Italy † O RI G IN A L U N ED IT ED M These authors contributed equally to this work. * Correspondence to: Sara N. Richter, E-mail: sara.richter@unipd.it; Marco Montagner, Email: marco.montagner@unipd.it; Graziano Martello, E-mail: graziano.martello@unipd.it © The Author(s) 2024. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Ilaria Frasson1,†, Linda Diamante1,2,†, Manuela Zangrossi1,†, Elena Carbognin2, Anna Dalla Pietà3, Alessandro Penna3, Antonio Rosato3,4, Ranieri Verin5, Filippo Torrigiani5, Cristiano Salata1, Marìa Paula Dizanzo1, Lorenzo Vaccaro6,7, Davide Cacchiarelli6,7,8, Sara N. Richter1,9,*, Marco Montagner1,*, Graziano Martello2,* Abstract The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants, some of which are resistant to vaccines and drugs targeting viral elements. Targeting host dependency factors, e.g. cellular proteins required for viral replication, would variants induce conserved cellular responses and exploit the same core host factors. To this end, we compared three variants of concern and found that the host transcriptional response was conserved, differing only in kinetics and magnitude. PT Through CRISPR screening, we identified host genes required for infection by each RI variant. Most of the genes were shared by multiple variants. We validated our hits with small molecules and repurposed Food and Drug Administration-approved drugs. SC All the drugs were highly active against all the variants tested, including new variants that emerged during the study (Delta and Omicron). Mechanistically, we identified U reactive oxygen species production as a key step in early virus replication. N Antioxidants such as N-acetyl cysteine (NAC) were effective against all the variants A in both human lung cells and a humanised mouse model. Our study supports the use M of available antioxidant drugs, such as NAC, as a general and effective..
{ 'indexed': {'date-parts': [[2024, 2, 2]], 'date-time': '2024-02-02T21:42:02Z', 'timestamp': 1706910122902}, 'reference-count': 0, 'publisher': 'Oxford University Press (OUP)', 'license': [ { 'start': { 'date-parts': [[2024, 2, 2]], 'date-time': '2024-02-02T00:00:00Z', 'timestamp': 1706832000000}, 'content-version': 'am', 'delay-in-days': 1, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:p>The high mutation rate of SARS-CoV-2 leads to the emergence of ' 'multiple variants, some of which are resistant to vaccines and drugs targeting viral ' 'elements. Targeting host dependency factors, e.g. cellular proteins required for viral ' 'replication, would help prevent resistance. However, it remains unclear whether different ' 'SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host ' 'factors. To this end, we compared three variants of concern and found that the host ' 'transcriptional response was conserved, differing only in kinetics and magnitude. Through ' 'CRISPR screening, we identified host genes required for infection by each variant. Most of ' 'the genes were shared by multiple variants. We validated our hits with small molecules and ' 'repurposed Food and Drug Administration-approved drugs. All the drugs were highly active ' 'against all the variants tested, including new variants that emerged during the study (Delta ' 'and Omicron). Mechanistically, we identified reactive oxygen species production as a key step ' 'in early virus replication. Antioxidants such as N-acetyl cysteine (NAC) were effective ' 'against all the variants in both human lung cells and a humanised mouse model. Our study ' 'supports the use of available antioxidant drugs, such as NAC, as a general and effective ' 'anti-COVID-19 approach.</jats:p>', 'DOI': '10.1093/jmcb/mjae004', 'type': 'journal-article', 'created': {'date-parts': [[2024, 2, 2]], 'date-time': '2024-02-02T05:44:42Z', 'timestamp': 1706852682000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of ' 'concern', 'prefix': '10.1093', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-5135-5707', 'authenticated-orcid': False, 'given': 'Ilaria', 'family': 'Frasson', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}]}, { 'given': 'Linda', 'family': 'Diamante', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}, { 'name': 'Department of Biology, Armenise/Harvard Pluripotent Stem Cell ' 'Biology Laboratory, University of Padua , Padua 35131 , Italy'}]}, { 'given': 'Manuela', 'family': 'Zangrossi', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}]}, { 'given': 'Elena', 'family': 'Carbognin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Biology, Armenise/Harvard Pluripotent Stem Cell ' 'Biology Laboratory, University of Padua , Padua 35131 , Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0002-7875-7914', 'authenticated-orcid': False, 'given': 'Anna', 'family': 'Dalla Pietà', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department. of Surgery, Oncology and Gastroenterology, ' 'University of Padua , Padua 35128 , Italy'}]}, { 'given': 'Alessandro', 'family': 'Penna', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department. of Surgery, Oncology and Gastroenterology, ' 'University of Padua , Padua 35128 , Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5263-8386', 'authenticated-orcid': False, 'given': 'Antonio', 'family': 'Rosato', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department. of Surgery, Oncology and Gastroenterology, ' 'University of Padua , Padua 35128 , Italy'}, {'name': 'Veneto Institute of Oncology IOV-IRCCS , Padua 35128 , Italy'}]}, { 'given': 'Ranieri', 'family': 'Verin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Comparative Biomedicine and Food Science, ' 'University of Padua , Padua 35020 , Italy'}]}, { 'given': 'Filippo', 'family': 'Torrigiani', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Comparative Biomedicine and Food Science, ' 'University of Padua , Padua 35020 , Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5136-7406', 'authenticated-orcid': False, 'given': 'Cristiano', 'family': 'Salata', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}]}, { 'given': 'Marìa Paula', 'family': 'Dizanzo', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}]}, { 'given': 'Lorenzo', 'family': 'Vaccaro', 'sequence': 'additional', 'affiliation': [ { 'name': 'Telethon Institute of Genetics and Medicine (TIGEM), ' 'Armenise/Harvard Laboratory of Integrative Genomics , Pozzuoli ' '80078 , Italy'}, { 'name': 'Department of Translational Medicine, Federico II University , ' 'Naples 80138 , Italy'}]}, { 'given': 'Davide', 'family': 'Cacchiarelli', 'sequence': 'additional', 'affiliation': [ { 'name': 'Telethon Institute of Genetics and Medicine (TIGEM), ' 'Armenise/Harvard Laboratory of Integrative Genomics , Pozzuoli ' '80078 , Italy'}, { 'name': 'Department of Translational Medicine, Federico II University , ' 'Naples 80138 , Italy'}, { 'name': 'School for Advanced Studies, Genomics and Experimental Medicine ' 'Program, University of Naples “Federico II” , Naples 80138 , ' 'Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0002-5446-9029', 'authenticated-orcid': False, 'given': 'Sara N', 'family': 'Richter', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}, { 'name': 'Microbiology and Virology Unit, Padua University Hospital , ' 'Padua 35128 , Italy'}]}, { 'given': 'Marco', 'family': 'Montagner', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Molecular Medicine, University of Padua , Padua ' '35121 , Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0001-5520-085X', 'authenticated-orcid': False, 'given': 'Graziano', 'family': 'Martello', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Biology, Armenise/Harvard Pluripotent Stem Cell ' 'Biology Laboratory, University of Padua , Padua 35131 , ' 'Italy'}]}], 'member': '286', 'published-online': {'date-parts': [[2024, 2, 1]]}, 'container-title': 'Journal of Molecular Cell Biology', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/jmcb/advance-article-pdf/doi/10.1093/jmcb/mjae004/56545101/mjae004.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/jmcb/advance-article-pdf/doi/10.1093/jmcb/mjae004/56545101/mjae004.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 2, 2]], 'date-time': '2024-02-02T05:44:42Z', 'timestamp': 1706852682000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://academic.oup.com/jmcb/advance-article/doi/10.1093/jmcb/mjae004/7596546'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 2, 1]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.1093/jmcb/mjae004', 'relation': {}, 'ISSN': ['1674-2788', '1759-4685'], 'subject': ['Cell Biology', 'Genetics', 'Molecular Biology', 'General Medicine'], 'published': {'date-parts': [[2024, 2, 1]]}}
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit