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Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma

Zhou et al., PLOS ONE, doi:10.1371/journal.pone.0300441
Apr 2024  
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Quercetin for COVID-19
22nd treatment shown to reduce risk in July 2021
 
*, now known with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
In Silico study suggesting that quercetin and tetrandrine are potential treatments for COVID-19 and intrahepatic cholangiocarcinoma (ICC). Authors identify 70 shared differentially expressed genes between COVID-19 and ICC, indicating similarities in pathogenesis related to metabolism and immunity. Drug enrichment analysis pinpoints quercetin and tetrandrine as promising candidates that may treat both diseases.
In Silico studies predict inhibition of SARS-CoV-2, or minimization of side effects, with quercetin or metabolites via binding to the spike Note A, Alavi, Azmi (B), Chandran, Kandeil, Mandal, Moschovou, Nguyen, Pan, Thapa (B), Şimşek, Mpro Note B, Akinwumi, Alanzi, Ibeh, Kandeil, Mandal, Moschovou, Nguyen, Qin, Rehman, Sekiou (B), Singh, Thapa (B), Wang, Zhang, Shaik, Waqas, Nalban, Irfan, RNA-dependent RNA polymerase Note C, Corbo, PLpro Note D, Ibeh, Zhang, ACE2 Note E, Chandran, Ibeh, Qin, Thapa (B), Şimşek, Alkafaas, TMPRSS2 Note F, Chandran, helicase Note G, Alanzi, Singh (B), endoribonuclease Note H, Alavi, cathepsin L Note I, Ahmed, Wnt-3 Note J, Chandran, FZD Note K, Chandran, LRP6 Note L, Chandran, ezrin Note M, Chellasamy, ADRP Note N, Nguyen, NRP1 Note O, Şimşek, EP300 Note P, Hasanah, PTGS2 Note Q, Qin, HSP90AA1 Note R, Qin, Hasanah, matrix metalloproteinase 9 Note S, Sai Ramesh, IL-6 Note T, Yang, Yang (B), IL-10 Note U, Yang, VEGFA Note V, Yang (B), and RELA Note W, Yang (B) proteins. In Vitro studies demonstrate efficacy in Calu-3 Note X, DiGuilio, A549 Note Y, Yang, HEK293-ACE2+ Note Z, Singh (C), Huh-7 Note AA, Pan, Caco-2 Note AB, Roy, Vero E6 Note AC, Kandeil, El-Megharbel, Roy, mTEC Note AD, Wu, and RAW264.7 Note AE, Wu cells. Animal studies demonstrate efficacy in K18-hACE2 mice Note AF, Aguado, db/db mice Note AG, Wu, Wu (B), BALB/c mice Note AH, Shaker, and rats El-Megharbel (B). Quercetin reduced proinflammatory cytokines and protected lung and kidney tissue against LPS-induced damage in mice Shaker.
Zhou et al., 22 Apr 2024, peer-reviewed, 10 authors. Contact: ykf13@163.com.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperQuercetinAll
Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma
Xinyi Zhou, Tengda Huang, Hongyuan Pan, Ao Du, Tian Wu, Jiang Lan, Yujia Song, Yue Lv, Fang He, Kefei Yuan
PLOS ONE, doi:10.1371/journal.pone.0300441
Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. Methods With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. Results This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodateoxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine,
Supporting information S1
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Nonetheless, few studies have investigated the impact of COVID-19 on ' 'ICC patients.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec002">\n' '<jats:title>Methods</jats:title>\n' '<jats:p>With the methods of systems biology and bioinformatics, this study explored the link ' 'between COVID-19 and ICC, and searched for potential therapeutic drugs.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec003">\n' '<jats:title>Results</jats:title>\n' '<jats:p>This study identified a total of 70 common differentially expressed genes (DEGs) ' 'shared by both diseases, shedding light on their shared functionalities. Enrichment analysis ' 'pinpointed metabolism and immunity as the primary areas influenced by these common genes. ' 'Subsequently, through protein-protein interaction (PPI) network analysis, we identified ' '<jats:italic>SCD</jats:italic>, <jats:italic>ACSL5</jats:italic>, ' '<jats:italic>ACAT2</jats:italic>, <jats:italic>HSD17B4</jats:italic>, ' '<jats:italic>ALDOA</jats:italic>, <jats:italic>ACSS1</jats:italic>, ' '<jats:italic>ACADSB</jats:italic>, <jats:italic>CYP51A1</jats:italic>, ' '<jats:italic>PSAT1</jats:italic>, and <jats:italic>HKDC1</jats:italic> as hub genes. ' 'Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to ' 'regulate the hub genes. 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