Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Abstract

The pandemic phase of coronavirus disease 2019 (COVID-19) appears to be over in most countries. However, the unexpected behaviour and unstable nature of coronaviruses, including temporary hiatuses, re-emergence, emergence of new variants, and changing outbreak epicentres during the COVID-19 pandemic, have been frequently reported. The mentioned trend shows the fact that in addition to vaccine development, different strategies should be considered to deal effectively with this disease, in long term. In this regard, the role of enzymes in regulating immune responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently attracted much attention. Moreover, several reports confirm the association of short telomeres with sever COVID-19 symptoms. This review highlights the role of several enzymes involved in telomere length (TL) regulation and explains their relevance to SARS-CoV-2 infection. Apparently, inhibition of telomere shortening (TS) through inhibition and/or activation of these enzymes could be a potential target in the treatment of COVID-19, which may also lead to a reduction in disease severity.

Keywords: Coronavirus disease-2019 (COVID-19); Immune responses; SARS-CoV-2 entry blockers; Telomerase activation; Telomerase inhibition; Telomere shortening.

Fig. 1

Schematic representation of viral entry in the presence of long and short telomeres as well as the association of telomere-related enzymes with SARS-CoV-2 infection LT Long telomeres, ST Short telomeres, ACE2 Angiotensin converting enzyme-2, DPP4 Dipeptidyl peptidase 4, TMPRSS2 Transmembrane protease serine protease-2, ATM Ataxia-telangiectasia mutated, ATR Ataxia-telangiectasia and Rad3, ALT Alanine aminotransferase, AST Aspartate aminotransferase, FASN Fatty acid synthase, LDHA Lactate dehydrogenase A, LDHB Lactate dehydrogenase B, : Activation of the enzyme is suggested, : Inhibition of the enzyme is suggested, : Coronavirus, : Blocking virus entry and mild infection of SARS-CoV-2 in the presence of long telomeres, : Easy viral entry and severe infection of SARS-CoV-2 in the presence of short telomeres, : chromosome and telomeres.*ALT and AST are not directly involved in the regulation of telomere length

Fig. 2

Schematic representation of paradoxical effects of telomerase inhibitors on telomeres and telomerase activity. Reproduced based on Valdiani et al. (2022) SM Specific modulation, NSM Non-specific modulation, ST Short telomeres, HTA High telomerase activity, RS Replicative senescence, RI Replicative immortality, TS Telomere shortening, NT Normal telomeres, LT Long telomeres or normal telomeres, NTA Normal telomerase activity, TM Telomere maintenance/elongation, LTA Low telomerase activity