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Background: The recent COVID-19 (coronavirus disease 2019) pandemic triggered research on the development of new vaccines/drugs, repurposing of clinically approved drugs, and assessment of natural anti-COVID-19 compounds. Based on the gender difference in the severity of the disease, such as a higher number of men hospitalized and in intense care units, variations in sex hormones have been predicted to play a role in disease susceptibility. Cell surface receptors (Angiotensin-Converting Enzyme 2; ACE2 and a connected transmembrane protease serine 2- TMPSS2) are upregulated by androgens. Conversely, androgen antagonists have also been shown to lower ACE2 levels, implying their usefulness in COVID-19 management.
Objectives: In this study, we performed computational and cell-based assays to investigate the anti- COVID-19 potential of Withaferin-A and Caffeic acid phenethyl ester, natural compounds from and honeybee propolis, respectively.
Methods: Structure-based computational approach was adopted to predict binding stability, interactions, and dynamics of the two test compounds to three target proteins (androgen receptor, ACE2, and TMPRSS2). Further, , cell-based experimental approaches were used to investigate the effect of compounds on target protein expression and SARS-CoV-2 replication.
Results: Computation and experimental analyses revealed that (i) CAPE, but not Wi-A, can act as androgen antagonist and hence inhibit the transcriptional activation function of androgen receptor, (ii) while both Wi-A and CAPE could interact with ACE2 and TMPRSS2, Wi-A showed higher binding affinity, and (iii) combination of Wi-A and CAPE (Wi-ACAPE) caused strong downregulation of ACE2 and TMPRSS2 expression and inhibition of virus infection.
Conclusion: Wi-A and CAPE possess multimodal anti-COVID-19 potential, and their combination (Wi-ACAPE) is expected to provide better activity and hence warrant further attention in the laboratory and clinic.
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http://dx.doi.org/10.2174/0115680266280720231221100004 | DOI Listing |
Curr Res Microb Sci
November 2024
Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
The global COVID-19 pandemic, which began in 2019, is still ongoing. SARS-CoV-2, also known as the severe acute respiratory syndrome coronavirus 2, is the causative agent. Diarrhea, nausea, and vomiting are common GI symptoms observed in a significant number of COVID-19 patients.
View Article and Find Full Text PDFCell Biosci
December 2024
Division of Neuroscience, Dept. of Psychology, University La Sapienza, Via dei Sardi 70, 00185, Rome, Italy.
Background: The Niemann Pick C1 (NPC1) protein is an intracellular cholesterol transporter located in the late endosome/lysosome (LE/Ly) that is involved in the mobilization of endocytosed cholesterol. Loss-of-function mutations in the NPC1 gene lead to the accumulation of cholesterol and sphingolipids in LE/Ly, resulting in severe fatal NPC1 disease. Cellular alterations associated with NPC1 inactivation affect both the integrity of lipid rafts and the endocytic pathway.
View Article and Find Full Text PDFJ Assist Reprod Genet
December 2024
Department of Gynecology, Division of Gynecology and Reproductive Medicine, Fertility Center, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy.
Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind the COVID-19 pandemic, affects multiple organs, including the male reproductive system. While viral infections can harm male fertility through cytokine storms, the effects of SARS-CoV-2 on fertility are still unclear. Thus, this study aimed to examine the persistence of viral RNA and inflammatory responses in semen following SARS-CoV-2 infection and the safety of conventional freezing and vitrification techniques.
View Article and Find Full Text PDFClin Sci (Lond)
December 2024
Institute for Medical Virology, Department of Molecular Virology, University Hospital Tuebingen,, Tübingen, Germany.
PLoS One
December 2024
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Research on SARS-CoV-2, the viral pathogen that causes COVID-19, has identified angiotensin converting enzyme 2 (ACE2) as the primary viral receptor. Several genes that encode viral cofactors, such as TMPRSS2, NRP1, CTSL, and possibly KIM1, have since been discovered. Glutamyl aminopeptidase (APA), encoded by the gene ENPEP, is another cofactor candidate due to similarities in its biological role and high correlation with ACE2 and other human coronavirus receptors, such as aminopeptidase N (APN) and dipeptidyl peptidase 4 (DPP4).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!