ArticleAntiviral research2022
S-adenosylmethionine-dependent methyltransferase inhibitor DZNep blocks transcription and translation of SARS-CoV-2 genome with a low tendency to select for drug-resistant viral variants.
Article in Antiviral research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
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- SRSF3 and hnRNP A1-mediated m6A-modified circCDK14 regulates intramuscular fat deposition by acting as miR-4492-z sponge.Cellular & molecular biology letters · 2025Article
- Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or mNature communications · 2025Article
- RNA Modifications in Pathogenic Viruses: Existence, Mechanism, and Impacts.Microorganisms · 2024Review
- Cannabinoid-Inspired Inhibitors of the SARS-CoV-2 Coronavirus 2'-Molecules (Basel, Switzerland) · 2024Article
- Sulfoglycodendron Antivirals with Scalable Architectures and Activities.Journal of chemical information and modeling · 2024Article
- Sulfoglycodendron Antivirals with Scalable Architectures and Activities.bioRxiv : the preprint server for biology · 2024Article
- p38-MAPK is prerequisite for the synthesis of SARS-CoV-2 protein.Virusdisease · 2024Article
- Coronavirus 2'-O-methyltransferase: A promising therapeutic target.Virus research · 2023Review
- Article
- Role of ROCK signaling in virus replication.Virus research · 2023Review
- The risk of COVID-19 can be predicted by a nomogram based on m6A-related genes.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2022Article
- ROCK1/MLC2 inhibition induces decay of viral mRNA in BPXV infected cells.Scientific reports · 2022Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the in vitro antiviral activity of DZNep (3-Deazaneplanocin A; an inhibitor of S-adenosylmethionine-dependent methyltransferase) against SARS-CoV-2, besides demonstrating its protective efficacy against lethal infection of infectious bronchitis virus (IBV, a member of the Coronaviridae family). DZNep treatment resulted in reduced synthesis of SARS-CoV-2 RNA and proteins without affecting other steps of viral life cycle. We demonstrated that deposition of N6-methyl adenosine (m6A) in SARS-CoV-2 RNA in the infected cells recruits heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), an RNA binding protein which serves as a m6A reader. DZNep inhibited the recruitment of hnRNPA1 at m6A-modified SARS-CoV-2 RNA which eventually suppressed the synthesis of the viral genome. In addition, m6A-marked RNA and hnRNPA1 interaction was also shown to regulate early translation to replication switch of SARS-CoV-2 genome. Furthermore, abrogation of methylation by DZNep also resulted in defective synthesis of the 5' cap of viral RNA, thereby resulting in its failure to interact with eIF4E (a cap-binding protein), eventually leading to a decreased synthesis of viral proteins. Most importantly, DZNep-resistant mutants could not be observed upon long-term sequential passage of SARS-CoV-2 in cell culture. In summary, we report the novel role of methylation in the life cycle of SARS-CoV-2 and propose that targeting the methylome using DZNep could be of significant therapeutic value against SARS-CoV-2 infection.
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