ABSTRACT
The serine/threonine p21-activating PAK kinases which act as important mediators of the Rho family of GTPases (Rho GTPases) Cdc42ĝ€¢GTP and Racĝ€¢GTP. PAK1 is one of the key molecules in the regulation of cytoskeletal actin assembly, phenotypic signaling, gene expression, and directly affects many cellular processes such as cell motility, invasion, metastasis, cell growth, angiogenesis, cell cycle progression. To date, several sulphated steroidal saponins have been reported to block the PAK1-dependent growth of A549 lung cancer. In this study, we investigated molecular interactions of N-triterpene saponins and PAK1 in silico molecular docking, and further evaluated the binding affinities. Molecular docking simulation was performed through AutoDock 4.2.2. an automated docking tool. We found that N-triterpene saponin 2 had the higher binding affinity towards PAK1 targeted protein. To the best of our knowledge, no report on N-triterpene saponins as a PAK1 inhibitor. © 2022 ACM.
ABSTRACT
OBJECTIVE: The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), poses several catastrophic threat s globally including those on economy, lifestyle and health. Although the respiratory tract is the primary proliferation site of the virus, its effects on other organs and organ systems is devastating. One of the potential tar-gets for SARS-CoV-2 invasion is the male reproductive system owing to the presence of viral receptors i.e., ACE2 and TMPRSS2 in the testis. Currently there are differing views in literature on whether SARS-CoV-2 infection has any short term and long term effects on male fertility. This pilot study was aimed to assess the impact of viral infection on crucial reproductive processes at the molecular level even after recovery. MATERIALS AND METHODS: We performed a label free quantitative proteomic analysis of semen procured from 17 COVID-19 recovered and 10 healthy fertile individuals using high resolution mass spectrometry. RESULTS: Our proteomic analysis resulted in the identification of 48 differentially expressed proteins of which 27 were upregulated and 21 were downregulated in recovered individuals. Further bio-informatic analysis revealed the dysregulation of several biological processes linked to male reproductive functions. Pathways like regulation of cell motility, regulation of adhesion, sperm-egg recognition, response to testosterone, extracellular matrix adhesion and endopeptidase activity were found to be downregulated in the recovered group. Moreover, the down regulation of two candidate proteins;Semenogelin 1 and Prosaposin which are related to male fertility were also validated using targeted proteomic approach CONCLUSIONS: This extensive proteomic study sheds light on the possible effects of SARS-CoV2 infection on reproductive functions and subsequently on male fertility even after apparent recovery from viral infection. IMPACT STATEMENT: The semen proteomic analysis of the COVID-19 recovered patients portrays a clear scenario of alteration of reproductive function in response to viral infection after clinical recovery, thus corroborating a possibility of virus-mediated impact on male infertility. A similar kind of study on large cohort will also direct the way to combat the viral effect on male reproductive function. This study would guide clinicians in counselling couples affected by COVID-19 as to the possible short term and long term effects on male reproductive potential.