Table 2 Summary of research on m⁶A modification in SARS-CoV-2 and associated sequencing technologies

The architecture of SARS-CoV-2 genome inside virion

25

Nanopore DRS

The tertiary structure of the SARS-CoV-2 RNA genome was reconstructed, revealing an “unentangled globule” conformation

[62]

Role of host m⁶A machinery in coronavirus replications

14

MeRIP-seq

Depletion of METTL3 or reader protein could suppress SARS-Cov-2’s replication, indicating the therapeutic potential of targeting the m⁶A pathway to restrict coronavirus reproduction

[66]

Regulation of viral m⁶A RNA modification and host immune response

6–16

MeRIP-seq

SARS-CoV-2 genomic RNA contains m⁶A modifications enriched in the 3′ end region. Depletion of METTL3 decreases m⁶A levels in SARS-Cov-2 and host genes, impacting the innate immune signaling pathway and inflammatory gene expression

[14]

m⁶A epitranscriptome of SARS-CoV-2 genomic RNA

15

Nanopore DRS

m⁶A modification could influence the virus’s ability to evade the immune system and vary among different viral variants

[72]

Role of m⁶A modification in SARS-CoV-2 and how it is modulated by host m⁶A machinery

5 based on MeRIP-seq;

8–14 based on Nanopore sequencing in different cells lines

MeRIP-seq and Nanopore DRS

SARS-CoV-2 RNA contains m⁶A modifications influenced by METTL3. Alterations in METTL3 expression changed the virus’s replication, and the viral protein RdRp was found to interact with METTL3, influencing its distribution and posttranslational modifications

[73]

m⁶A epitranscriptome of SARS-CoV-2 in host cell

8

Combined RIP-seq and miCLIP

SARS-CoV-2 infection triggered a global increase in host m⁶A methylome, exhibiting altered localization and motifs of m⁶A methylation in mRNAs

[15]

Examines how RBM15, an m⁶A methyltransferase, influences COVID-19 severity

N/A

MeRIP-seq

RBM15 promoted the expression of functional genes by elevating m⁶A modification, suggesting RBM15’s modulation of m⁶A modification is a significant factor in COVID-19’s pathogenesis and could be a potential therapeutic target

[68]

Analyze the m⁶A methylome of SARS-CoV-2 and the potential regulatory role of m⁶A in SARS-CoV-2 RNA abundance

11

MeRIP-seq

m⁶A might regulate abundance of SARS-CoV-2 through a mechanism of 3′ UTR with or without RRACH

[67]

Role of FTO during SARS-Cov-2 infections, and how this correlates with the severity of COVID-19 in patients

3

m⁶A-seq

FTO has a significant impact on m⁶A marking on SARS-CoV-2 and may affect the severity of COVID-19

[71]

Exploring how m⁶A RNA modification in host cells is altered during SARS-CoV-2 infection

5

MeRIP-seq

Define the m⁶A modification profile in infected versus uninfected cells, identifying various mRNA and noncoding RNA species with differential m⁶A modification in response to SARS-CoV-2

[69]

Impact of SARS-CoV-2 infection on cellular m⁶A RNA methylation and its subsequent effects on host cell gene expression and stress response mechanisms

Average 10

Refined MeRIP-seq

Infection with various SARS-CoV-2 variants results in a widespread decrease in m⁶A RNA methylation in host cells, disrupting normal cellular processes and stress responses, with variant-specific differences observed in the extent of these effects

[70]