Identification of host transcriptome-guided repurposable drugs for SARS-CoV-1 infections and their validation with SARS-CoV-2 infections by using the integrated bioinformatics approaches

PLoS ONE, Год журнала: 2022, Номер 17(4), С. e0266124 - e0266124

Опубликована: Апрель 7, 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is one of the most severe global pandemic due to its high pathogenicity and death rate starting from end 2019. Though there are some vaccines available against SAER-CoV-2 infections, we worried about their effectiveness, unstable sequence patterns. Therefore, beside vaccines, globally effective supporting drugs also required for treatment SARS-CoV-2 infection. To explore commonly repurposable different variants coronavirus in this article, an attempt was made host genomic biomarkers guided SARS-CoV-1 infections validation with by using integrated bioinformatics approaches. At first, identified 138 differentially expressed genes (DEGs) between infected control samples analyzing throughput gene-expression profiles select drug target key receptors. Then top-ranked 11 DEGs (SMAD4, GSK3B, SIRT1, ATM, RIPK1, PRKACB, MED17, CCT2, BIRC3, ETS1 TXN) as hub (HubGs) protein-protein interaction (PPI) network analysis highlighting functions, pathways, regulators linkage other disease risks that may influence infections. The DEGs-set enrichment significantly detected crucial biological processes (immune response, regulation angiogenesis, apoptotic process, cytokine production programmed cell death, response hypoxia oxidative stress), molecular functions (transcription factor binding oxidoreductase activity) pathways (transcriptional mis-regulation cancer, chemokine signaling pathway) associated well involving HubGs. gene regulatory (GRN) transcription factors (FOXC1, GATA2, YY1, FOXL1, TP53 SRF) micro-RNAs (hsa-mir-92a-3p, hsa-mir-155-5p, hsa-mir-106b-5p, hsa-mir-34a-5p hsa-mir-19b-3p) transcriptional post- HubGs, respectively. We chemicals (Valproic Acid, Cyclosporine, Copper Sulfate arsenic trioxide) regulates disease-HubGs showed our predicted HubGs several diseases including types lung diseases. considered mediated proteins 6 TFs (receptors) performed docking 3CL protease-guided top listed 90 anti-viral out 3410. found Rapamycin, Tacrolimus, Torin-2, Radotinib, Danoprevir, Ivermectin Daclatasvir 7 candidate-drugs respect proposed Then, validated these already published simulation significant affinity scores candidate-drugs. Finally, all findings literature review. might play a vital role comorbidities, since comorbidities.

Язык: Английский

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The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 – A formulator’s perspective

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 148, С. 112767 - 112767

Опубликована: Фев. 28, 2022

With an increased transmissibility but milder form of disease the omicron variant COVID-19 and newer antivirals often still out reach many populations, a refocus current treatment regimens is required. Safe, affordable, available adjuvant treatments should also be considered known drugs substances need to repurposed tested. Resveratrol, well-known antioxidant natural origin, shown act as antiviral well playing role in immune stimulation, down regulation pro-inflammatory cytokine release reducing lung injury by oxidative stress, such option. New initiatives collaborations will however found unleash resveratrol's full potential pharmaceutical market.

Язык: Английский

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Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity

Clinical Epigenetics, Год журнала: 2021, Номер 13(1)

Опубликована: Окт. 11, 2021

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) and neuropilin-1 (NRP1) receptors for entry into cells, serine protease TMPRSS2 S protein priming. Inhibition of activity or engagement with ACE2 NRP1 has been shown to be an effective strategy blocking infectivity viral spreading. Valproic acid (VPA; 2-propylpentanoic acid) is epigenetic drug approved clinical use. It produces potent antiviral anti-inflammatory effects through its function as a histone deacetylase (HDAC) inhibitor. Here, we propose VPA potential candidate tackle COVID-19, in which rapid spread replication, hyperinflammation are crucial elements.We used diverse cell lines (HK-2, Huh-7, HUVEC, Caco-2, BEAS-2B) analyze effect other HDAC inhibitors on expression ACE-2 NRP-1 their ability inhibit infectivity, production, inflammatory response. Treatment significantly reduced host proteins all mechanism mediated by inhibitory activity. The maintained after infection. Consequently, treatment cells before infection impairs production infectious viruses, but not that ACE2- NRP1-independent viruses (VSV HCoV-229E). Moreover, addition 1 h post-infection reduces dose-dependent manner without modifying genomic subgenomic messenger RNAs (gRNA sg mRNAs) levels N protein. cytokines (TNF-α IL-6) induced TNF-α diminished presence VPA.Our data showed blocks three essential processes determining severity COVID-19. downregulates NRP1, reducing SARS-CoV-2; it decreases yields, probably because affects virus budding virions stability; dampens triggered Thus, administering could considered safe COVID-19 patients until vaccines have rolled out across world.

Язык: Английский

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Prospective Pharmacological Potential of Resveratrol in Delaying Kidney Aging

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(15), С. 8258 - 8258

Опубликована: Июль 31, 2021

Aging is an unavoidable part of life. The more aged we become, the susceptible become to various complications and damages vital organs, including kidneys. existing drugs for kidney diseases are mostly synthetic origins; thus, natural compounds with minimal side-effects have attracted growing interest from scientific community pharmaceutical companies. A literature search was carried out collect published research information on effects resveratrol aging. Recently, has emerged as a potential anti-aging agent. This versatile polyphenol exerts its by intervening in pathologies multi-signaling systems, sirtuin type 1, AMP-activated protein kinase, nuclear factor-κB. Researchers trying figure detailed mechanisms possible resveratrol-mediated interventions divergent pathways at molecular level. review highlights (i) causative factors implicated aging therapeutic aspects resveratrol, (ii) effectiveness delaying process while minimizing all side effects.

Язык: Английский

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Potential of Polyphenols to Restore SIRT1 and NAD+ Metabolism in Renal Disease

Nutrients, Год журнала: 2022, Номер 14(3), С. 653 - 653

Опубликована: Фев. 3, 2022

SIRT1 is an NAD+-dependent class III histone deacetylase that abundantly expressed in the kidney, where it modulates gene expression, apoptosis, energy homeostasis, autophagy, acute stress responses, and mitochondrial biogenesis. Alterations activity NAD+ metabolism are frequently observed chronic kidney diseases of diverse origins, including obesity diabetes. Nevertheless, vitro vivo studies clinical trials with humans show SIRT1-activating compounds derived from natural sources, such as polyphenols found fruits, vegetables, plants, resveratrol, quercetin, isoflavones, can prevent disease be part treatments for a wide variety diseases. Here, we summarize roles renal pathophysiology provide overview have potential to restore

Язык: Английский

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