ADP-ribosylhydrolases: from DNA damage repair to COVID-19

Abstract

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).

Integrated Analysis of microRNAs and Metabolomics in Rat’s Serum Reveals Multi-action Modes of Qingfei Paidu Decoction for COVID-19 Treatment

“…On one hand, among the top 100 predicted target genes of DEMs, 42% (42/100) have been reported to be involved in regulation of at least 33 kinds of virus infection (Additional le 10). Especially, Fasn, Adprh, VPS39, Scnn1α, Slc6a19, Ccr9 may facilitate SARS-CoV-2 infection [100][101][102][103] or be related to symptoms, like intestinal in ammation and nutritional status [104][105][106][107][108], respiratory conditions [109] or respiratory failure [110,111] in COVID-19 patients, and Wnk1 could ght against cytokine storm caused by sepsis in COVID-19 patient [112]. Their down-or up-regulations by corresponding miRNAs [19] can play a positive role in the treatment of COVID-19 with QFPDD.…”

“…Especially, seven target genes might facilitate SARS-CoV-2 infection [100][101][102][103] or be related to symptoms of COVID-19 [104][105][106][107][108][109][110][111][112], including fatty acid synthase (Fasn) [100], VPS39 HOPS complex subunit (Vps39) [101,102], sodium channel epithelial 1 alpha subunit (Scnn1α or ENaC-α) [109,113], solute carrier family 6 member 19 (Slc6a19 or B 0 AT1) [104][105][106][107][108], ADP-ribosylarginine hydrolase (Adprh) [103], C-C motif chemokine receptor 9 (Ccr9) [110,111], WNK lysine de cient protein kinase 1 (Wnk1) [112]. Fasn, VPS39 and Adprh may be required for SARS-CoV-2 replication [100,103] or infection [101,102]. ENaC-α, B 0 AT1 and CCR9 were strategically mimicked or regulated by SARS-CoV-2 infection, leading to respiratory symptoms or respiratory failure [109][110][111], intestinal in ammation and nutritional status [104][105][106][107][108] in COVID-19 patients.…”

“…The top 100 regulated genes ranked by score were speci cally selected out for further analysis, of which 42% (42/100) were reported to be involved in regulation of at least one kind of virus infection (Additional le 10). Especially, seven target genes might facilitate SARS-CoV-2 infection [100][101][102][103] or be related to symptoms of COVID-19 [104][105][106][107][108][109][110][111][112], including fatty acid synthase (Fasn) [100], VPS39 HOPS complex subunit (Vps39) [101,102], sodium channel epithelial 1 alpha subunit (Scnn1α or ENaC-α) [109,113], solute carrier family 6 member 19 (Slc6a19 or B 0 AT1) [104][105][106][107][108], ADP-ribosylarginine hydrolase (Adprh) [103], C-C motif chemokine receptor 9 (Ccr9) [110,111], WNK lysine de cient protein kinase 1 (Wnk1) [112]. Fasn, VPS39 and Adprh may be required for SARS-CoV-2 replication [100,103] or infection [101,102].…”

Informatization of National Public Service Fitness in Constructing a Smart City Using Big Data

“…On this fitness service platform, the public can search relevant information such as fitness venues, fitness equipment, and activity equipment. Relevant personnel on the service platform use the service to obtain points, which can be consumed after superposition [7,8].…”

“…x t � x t−1 + v t . 􏼨 (7) In formula (7), v t represents the running speed of the fitness behavior particles, x t represents the fitness value of particles, c 1 and c 2 represent the optimal learning operator, and rand 1 and rand 2 represent the random number between [0, 1], respectively. e objective function of constructing the statistical decision-making of the national fitness behavior data mining is expressed as given by the following formula:…”