School Of Health Sciences

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Browsing School Of Health Sciences by Subject "ACE2"

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    Contributions of human ACE2 and TMPRSS2 in determining host�pathogen interaction of COVID-19
    (Springer, 2021-02-25T00:00:00) Senapati, Sabyasachi; Banerjee, Pratibha; Bhagavatula, Sandilya; Kushwaha, Prem Prakash; Kumar, Shashank
    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is at present an emerging global public health crisis. Angiotensin converting enzyme 2 (ACE2) and trans-membrane protease serine 2 (TMPRSS2) are the two major host factors that contribute to the virulence of SARS-CoV-2 and pathogenesis of coronavirus disease-19 (COVID-19). Transmission of SARS-CoV-2 from animal to human is considered a rare event that necessarily requires strong evolutionary adaptations. Till date no other human cellular receptors are identified beside ACE2 for SARS-CoV-2 entry inside the human cell. Proteolytic cleavage of viral spike (S)-protein and ACE2 by TMPRSS2 began the entire host�pathogen interaction initiated with the physical binding of ACE2 to S-protein. SARS-CoV-2 S-protein binds to ACE2 with much higher affinity and stability than that of SARS-CoVs. Molecular interactions between ACE2-S and TMPRSS2-S are crucial and preciously mediated by specific residues. Structural stability, binding affinity and level of expression of these three interacting proteins are key susceptibility factors for COVID-19. Specific protein�protein interactions (PPI) are being identified that explains uniqueness of SARS-CoV-2 infection. Amino acid substitutions due to naturally occurring genetic polymorphisms potentially alter these PPIs and poses further clinical heterogeneity of COVID-19. Repurposing of several phytochemicals and approved drugs against ACE2, TMPRSS2 and S-protein have been proposed that could inhibit PPI between them. We have also identified some novel lead phytochemicals present in Azadirachta indica and Aloe barbadensis which could be utilized for further in vitro and in vivo anti-COVID-19 drug discovery. Uncovering details of ACE2-S and TMPRSS2-S interactions would further contribute to future research on COVID-19. � 2021, Indian Academy of Sciences.
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    In silico phytochemical repurposing of natural molecules as entry inhibitors against RBD of the spike protein of SARS-CoV-2 using molecular docking studies
    (Inderscience Publishers, 2023-04-18T00:00:00) Gupta, Pawan; Gupta, Swati; Sinha, Sukrat; Sundaram, Shanthy; Sharma, Vishnu K.; Munshi, Anjana
    The receptor binding domain (RBD) of Spike-protein (S-protein) is responsible for virus entry via interaction with host protein ACE2 (angiotensin-converting enzyme 2), present on the cell surface of humans. Therefore, S-protein is an important target to block the entry of the SARS-CoV-2 into the cell for further growth. In the present study, phytochemical repurposing of natural molecules: narirutin, naringin, neohesperidin and hesperidin were performed against the RBD S-protein/ACE2 interface as well as the RBD of the S-protein using molecular docking. These natural molecules were found to have structural similarity to each other and had binding potential against the viral infections. It is first time reported here that the naringin and narirutin are having binding potential against both RBD S-protein/ACE2 interface and active site of RBD of S-protein using binding mode analysis. Hence, this study will open avenues for multitargeting similar natural molecules binding against the SARS-CoV-2 proteins as all reports are made in this single study. Copyright � 2023 Inderscience Enterprises Ltd.