Table 1 Epigenetics involved in coronavirus infection and their therapeutic control

HDAC

Pan-HDAC class I and II

Affecting inflammatory functions and interferon response [45].

VPA + antivirals (remdesivir, ribavirin, favipiravir, galidesivir) or (rapamycin, selumetinib, trametinib)

or prostatin

Reduced pro-inflammatory mediator’s production and increased IL-10 production [55].

TSA + antivirals or

(rapamycin, selumetinib, trametinib)

Diminished genomes initiating gene replication, and induced the expression of cellular proteins responsible for viral inhibition [57].

SAHA + antivirals or (rapamycin, selumetinib, trametinib) or prostatin or BIX-01294 or DZNep

All HDAC classes including class I, II, and IV

Affecting EGFR/HER2 signaling, MAPK signaling, PI3K-Akt, and NFκB pathway [58].

Panobinostat + antivirals or (rapamycin, selumetinib, trametinib)

Enhanced TGF-β expression [58].

Belinostat or domatinostat + antivirals or (rapamycin, selumetinib, trametinib)

HKMT

Pan-HKMT EZH2

Attained cellular antiviral state and reduced viral yields [57].

DZNep + vorinostat

HKMT G9a

Enhancing antiviral state [57].

BIX-01294 + vorinostat

HMT Suv39H1

Permanent cell cycle arrest and RNA transcript blockage [59].

Suppressed IL-6 levels [60, 61].

Down-regulation of apoptosis, decrease in (N) protein expression, and RNA viral replication antagonism [51].

Counteracting hyper-inflammation: lowering pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokines, inducing IL-10 marker and TGF-β [58].

5-azadC + antivirals or (rapamycin, selumetinib, trametinib)

Viral mimicry [62].

Azacitidine + antivirals or (rapamycin, selumetinib, trametinib)

Clinical

ABBV-744, CPI-0610, RVX-208

BRD4 inhibition boosts a potential innate immune response, blocks viral attachment, inducts DNA damage response (DDR), decreases viral replication, and arrests cell-cycle with no apoptotic signs [63].

Preclinical

dBET6, JQ-1, MZ1