Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach

Ahmad, Ashfaq; Makhmutova, Zhandaulet; Cao, Wenwen; Majaz, Sidra; Amin, Amr; Xie, Yingqiu

doi:10.1080/14787210.2023.2179035

Cited by 8 publications

(4 citation statements)

References 56 publications

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“…Produces the wrapped form of virus that is required for cell‐to‐cell spread. Acts as a lipase with broad specificity including phospholipase C, phospholipase A, and triacylglycerol lipase activities 21,22 …”

Section: Resultsmentioning

confidence: 99%

Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain

Casimiro‐Soriguer,

Perez‐Florido,

Lara

et al. 2024

Health Science Reports

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Background and AimUntil the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non‐endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain.MethodsWhole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak.ResultsWhole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment.

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Section: Resultsmentioning

confidence: 99%

Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain

Casimiro‐Soriguer,

Perez‐Florido,

Lara

et al. 2024

Health Science Reports

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“…18 For instance, AMPK signaling may alter in NAFLD dependent on androgen receptor signaling, which is linked to immune response. 47,48 In healthy hepatocytes, AMPK controls the activity of enzymes involved in lipogenesis through phosphorylation and dephosphorylation. 49 Here, HFD or PA treatment lowered p-AMPK expression while increased p-p38 expression in mice liver tissues or AML-12 cells, which were reversed when Asprosin was downregulated, suggesting that inhibition of Asprosin might activate the AMPK-p38 signaling in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…AMPK, a key regulator of energy metabolism contributing to the energy of cell homeostasis, has been proposed as a potential therapeutic target of NAFLD 18 . For instance, AMPK signaling may alter in NAFLD dependent on androgen receptor signaling, which is linked to immune response 47,48 . In healthy hepatocytes, AMPK controls the activity of enzymes involved in lipogenesis through phosphorylation and dephosphorylation 49 .…”

Section: Discussionmentioning

confidence: 99%

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling

Zhang,

Lu,

Jiang

et al. 2023

Immunity Inflam & Disease

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BackgroundNonalcoholic fatty liver disease (NAFLD) is a primary contributor to liver‐related morbidity and mortality. Asprosin has been reported to be implicated in NAFLD.AimsThis work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism.Materials & MethodsThe weight of NAFLD mice induced by a high‐fat diet was detected. Quantitative reverse‐transcription polymerase chain reaction (RT‐qPCR) examined serum Asprosin expression. RT‐qPCR and western blot analysis examined Asprosin expression in mice liver tissues. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were implemented. Biochemical kits tested liver enzyme levels in mice serum and liver tissues. Hematoxylin and eosin staining evaluated liver histology. Liver weight was also tested and oil red O staining estimated lipid accumulation. RT‐qPCR and western blot analysis analyzed the expression of gluconeogenesis‐, fatty acid biosynthesis‐, fatty acid oxidation‐, and inflammation‐associated factors. Besides, western blot analysis examined the expression of AMP‐activated protein kinase (AMPK)/p38 signaling‐associated factors. In palmitic acid (PA)‐treated mice hepatocytes, RT‐qPCR and western blot analysis examined Asprosin expression. Lipid accumulation, gluconeogenesis, fatty acid biosynthesis, fatty acid oxidation, and inflammation were appraised again.ResultsAsprosin was overexpressed in the serum and liver tissues of NAFLD mice and PA‐treated mice hepatocytes. Asprosin interference reduced mice body and liver weight, improved glucose tolerance and diminished liver injury in vivo. Asprosin knockdown alleviated lipid accumulation and inflammatory infiltration both in vitro and in vivo. Additionally, Asprosin absence activated AMPK/p38 signaling and AMPK inhibitor Compound C reversed the impacts of Asprosin on lipid accumulation and inflammatory response.ConclusionCollectively, Asprosin inhibition suppressed lipid accumulation and inflammation to obstruct NAFLD through AMPK/p38 signaling.

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“…Furthermore, it has been identified a co-expression of ACE2 , TMPRSS2 , and AR in human alveolar and bronchial epithelial cells, indicating that AR drives ACE2 and TMPRSS2 expression in the lung [ 12 ]. Likewise, recent data have suggested AR as anti-infective target for anti-Omicron lineages, mainly due to the specificity of AR against spike RBD (receptor binding protein) of S AR S-CoV -2 [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity

Martinez-Diz,

Morales-Álvarez,

Garcia-Iglesias

et al. 2023

Hum Genomics

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Background The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms. Methods A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria. Results We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10–3), acting as proteases (p = 0.047). Conclusions In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease. Graphical abstract

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Androgen receptor, a possible anti-infective therapy target and a potent immune respondent in SARS-CoV-2 spike binding: a computational approach

Cited by 8 publications

References 56 publications

Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain

Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling

Analyzing the role of ACE2, AR, MX1 and TMPRSS2 genetic markers for COVID-19 severity

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