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Table 1 Epigenetics involved in coronavirus infection and their therapeutic control

From: Management of epigenomic networks entailed in coronavirus infections and COVID-19

Epigenetic drug target Antagonism “inhibitors” Potential outcome Combination therapy(few require clinical validation)
HDAC Pan-HDAC class I and II VPA Affecting inflammatory functions and interferon response [45]. VPA + antivirals (remdesivir, ribavirin, favipiravir, galidesivir) or (rapamycin, selumetinib, trametinib)
or prostatin
TSA Reduced pro-inflammatory mediator’s production and increased IL-10 production [55]. TSA + antivirals or
(rapamycin, selumetinib, trametinib)
Vorinostat (SAHA) 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 Panobinostat Affecting EGFR/HER2 signaling, MAPK signaling, PI3K-Akt, and NFκB pathway [58]. Panobinostat + antivirals or (rapamycin, selumetinib, trametinib)
Belinostat and domatinostat Enhanced TGF-β expression [58]. Belinostat or domatinostat + antivirals or (rapamycin, selumetinib, trametinib)
HKMT Pan-HKMT EZH2 DZNep Attained cellular antiviral state and reduced viral yields [57]. DZNep + vorinostat
HKMT G9a BIX-01294 Enhancing antiviral state [57]. BIX-01294 + vorinostat
HMT Suv39H1 Chaetocin Permanent cell cycle arrest and RNA transcript blockage [59].  
HAT Anacardic acid, MG149, C646 Suppressed IL-6 levels [60, 61].  
DNMT Resveratrol 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)
Azacitidine Viral mimicry [62]. Azacitidine + antivirals or (rapamycin, selumetinib, trametinib)
BET proteins (BRD4) 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