In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.

Histone-modifying enzymes and histone post-translational modifications (PTMs) play key roles in the organization (euchromatin versus heterochromatin) and function (active versus silenced genes) of chromatin. The abundance and activity of these enzymes, along with their associated histone PTMs, are often altered in cancer cells, leading to deregulated gene expression. The expression of the KMT2A-MLLT3 protein, resulting from a chromosomal translocation in mixed-lineage leukemia (MLL), a subtype of acute myeloid leukemia, augments transcription elongation, promoting the expression of HOXA9 and MEIS1, genes that play critical roles in MLL development. Bortezomib, a proteasome inhibitor, has been effective at treating various cancers. In this study, we compared the impact of bortezomib on histone PTMs in the MLL cell line MOLM-13 and the chronic myeloid leukemic (CML) cell line K562. We report that MOLM-13 had a greater level of histone H2B monoubiquitinated at lysine 120 (H2BK120ub) and histone H3 dimethylated at lysine 79 (H3K79me2) (modifications involved in elongation) and similar levels of histone H2A monoubiquitinated at lysine 119 (H2AK119ub). Bortezomib treatment resulted in significant reductions in H2BK120ub and H2AK119ub levels, as well as in transcript levels of genes involved in MLL development.

Histone-modifying enzymes and histone post-translational modifications (PTMs) play key roles in the organization (euchromatin versus heterochromatin) and function (active versus silenced genes) of chromatin. The abundance and activity of these enzymes, along with their associated histone PTMs, are often altered in cancer cells, leading to deregulated gene expression. The expression of the KMT2A-MLLT3 protein, resulting from a chromosomal translocation in mixed-lineage leukemia (MLL), a subtype of acute myeloid leukemia, augments transcription elongation, promoting the expression of HOXA9 and MEIS1, genes that play critical roles in MLL development. Bortezomib, a proteasome inhibitor, has been effective in treating various cancers. In this study, we compared the impact of bortezomib on histone PTMs in the MLL cell line MOLM-13 and the chronic myeloid leukemic (CML) cell line K562. We report that MOLM-13 had a greater level of histone H2B monoubiquitinated at lysine 120 (H2BK120ub) and histone H3 dimethylated at lysine 79 (H3K79me2) (modifications involved in elongation) and similar levels of histone H2A monoubiquitinated at lysine 119 (H2AK119ub). Bortezomib treatment resulted in significant reductions in H2BK120ub and H2AK119ub levels, the loss of FAcilitates Chromatin Transcription (FACT) chromatin association in both cell lines, and the reduced transcript levels of genes involved in the development of MLL.