ArticleThe EMBO journal2022
Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2'-O-ribose methyltransferases.
Article in The EMBO journal, 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, 39 citations in OpenAlex.
- The capping arms race: evolutionary interplay between IFIT proteins and viral molecular mimicry.Molecular biology reports · 2026Review
- Mechanistic insights into the association and activation of the SARS-CoV-2 2'-O-Methyltransferase (NSP16).bioRxiv : the preprint server for biology · 2026Article
- Article
- LMP7 as a Target for Coronavirus Therapy: Inhibition by Ixazomib and Interaction with SARS-CoV-2 Proteins Nsp13 and Nsp16.Pathogens (Basel, Switzerland) · 2025Article
- TransFactor-prediction of pro-viral SARS-CoV-2 host factors using a protein language model.Bioinformatics (Oxford, England) · 2025Article
- Targeting G9a-miScience · 2025Article
- Evolutionary Origins and Functional Diversification of 2'-O-Methyltransferases: Insights from Phylogenetic and Structural Analysis.International journal of molecular sciences · 2025Article
- Article
- Perspective for Drug Discovery Targeting SARS Coronavirus Methyltransferases: Function, Structure and Inhibition.Journal of medicinal chemistry · 2024Review
- Protein Thermal Stability Changes Induced by the Global Methylation Inhibitor 3-Deazaneplanocin A (DZNep).Biomolecules · 2024Article
- Article
- Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA.Biochemical Society transactions · 2024Review
- Tubercidin inhibits PRRSV replication via RIG-I/NF-κB pathways and interrupting viral nsp2 synthesis.Microbiology spectrum · 2024Article
- Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections.Virus research · 2024Article
- Coronavirus 2'-O-methyltransferase: A promising therapeutic target.Virus research · 2023Review
- Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors.ACS infectious diseases · 2023Article
- MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake.Viruses · 2023Article
- Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.Signal transduction and targeted therapy · 2023Review
- Therapeutic strategies for COVID-19: progress and lessons learned.Nature reviews. Drug discovery · 2023Review
- SARS-CoV-2 Uses Nonstructural Protein 16 To Evade Restriction by IFIT1 and IFIT3.Journal of virology · 2023Article
Corrections and comments
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Authors and funding
29 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SARS-CoV-2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2'-O-ribose cap needed for viral immune escape. We find that the host cap 2'-O-ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS-CoV-2 replication. Using in silico target-based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti-SARS-CoV-2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co-substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID-19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection-induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID-19.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.