Methotrexate, an anti-inflammatory drug, inhibits Hepatitis E viral replication

Hepatitis E Virus (HEV) is a positively oriented RNA virus having a 7.2 kb genome. HEV consists of three open reading frames (ORF1-3). Of these, ORF1 codes for the enzymes Methyltransferase (Mtase), Papain-like cysteine protease (PCP), RNA helicase, and RNA-dependent RNA polymerase (RdRp). Unavailab...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2023-12, Vol.38 (1), p.2280500-2280500
Main Authors: Kumar, Akash, Hooda, Preeti, Puri, Anindita, Khatter, Radhika, S Al-Dosari, Mohammed, Sinha, Neha, Parvez, Mohammad K, Sehgal, Deepak
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents
antiviral
Binding sites
Cloning
Cysteine proteinase
DNA helicase
DNA-directed RNA polymerase
Double-stranded RNA
Energy
Enzymes
FDA approval
Gene regulation
Genomes
helicase
Hepatitis
Hepatitis E
Hepatitis E virus
Hepatitis E virus - genetics
Humans
Inflammation
Life sciences
Ligands
Methotrexate
Methyltransferase
mRNA processing
Open reading frames
Papain
Pharmacy
Post-transcription
Proteins
Replication
Ribavirin
RNA helicase
RNA polymerase
RNA processing
RNA replication
RNA viruses
RNA-directed RNA polymerase
Simulation
Unwinding
Virology
Virus Replication
Viruses
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Summary:Hepatitis E Virus (HEV) is a positively oriented RNA virus having a 7.2 kb genome. HEV consists of three open reading frames (ORF1-3). Of these, ORF1 codes for the enzymes Methyltransferase (Mtase), Papain-like cysteine protease (PCP), RNA helicase, and RNA-dependent RNA polymerase (RdRp). Unavailability of a vaccine or effective drug against HEV and considering the side effects associated with the off-label use of ribavirin (RBV) and pegylated interferons, an alternative approach is required by the modulation of specific enzymes to prevent the infection. HEV helicase is involved in unwinding the double-stranded RNA, RNA processing, transcriptional regulation, and pre-mRNA processing. Therefore, we screened FDA-approved compounds from the ZINC15 database against the modelled 3D structure of HEV helicase and found that methotrexate and compound A (Pubchem ID BTB07890) inhibit the NTPase and dsRNA unwinding activity leading to inhibition of HEV RNA replication. This may be further authenticated by study.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2023.2280500