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AN465: A Novel Therapeutic Targeting METTL3 Inhibition in Hand, Foot, and Mouth Disease

ABSTRACT: Abstract: Hand, foot, and mouth disease (HFMD) is a widespread viral infection predominantly affecting young children, for which specific therapies remain elusive despite extensive research efforts. N6-methyladenosine (m6A) modifications, prevalent in eukaryotic mRNA and long non-coding RNAs, are also found in various viral RNAs. A nuclear methyltransferase complex, including METTL3 as the catalytic subunit, catalyzes these m6A modifications co-transcriptionally, functioning as m6A 'writers'. Notably, enterovirus 71 (EV71) RNA undergoes m6A modification during infection, mediated by METTL3, influencing virus replication. We hypothesized that inhibiting METTL3 could directly suppress EV71 replication through m6A modifications. Despite the renown of STM2457 as a METTL3 inhibitor, our preliminary experiments indicated its ineffectiveness against EV71. Leveraging a compound library tenfold larger than that in STM2457's discovery, we identified AN465 as a potent METTL3 inhibitor. Through rigorous experiments and analyses, we demonstrate that AN465 surpasses STM2457 in inhibiting EV71 replication by effectively targeting METTL3. Our findings propose AN465 as a promising therapeutic candidate for combating HFMD by curbing EV71 replication.

ORGANISM(S): Homo sapiens

PROVIDER: GSE291299 | GEO | 2026/03/21

REPOSITORIES: GEO

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