Introduction to Human Angiotensin Converting

Antibodies that interfere with SARS-CoV-2 spike function—in particular, antibodies that prevent the interaction between the receptor binding domain (RBD) of spike and human angiotensin-converting enzyme 2 (ACE2), the canonical receptor on the host cell surface—can neutralize the virus in vitro and are associated with protection from infection in vivo (1).

In this review, we discuss some important characteristics of the main SARS‑CoV‑2 surface antigen, the spike (S) protein, such as (i) ability of the receptor-binding domain (RBD) to switch between the “standing-up” position (open pre-fusion conformation) for receptor binding and the “lying-down” position (closed pre-fusion conformation) for immune system evasion; (ii) advantage of a high binding affinity of the RBD open conformation to the human angiotensin-converting enzyme 2 (ACE2) receptor for efficient cell entry; and (iii) S protein preliminary activation by the intracellular furin-like proteases for facilitation of the virus spreading across different cell types.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2– and SARS-CoV–induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2–inoculated human angiotensin-converting enzyme 2 (hACE2) mice.

Human angiotensin-converting enzyme 2 (ACE 2) receptor is considered the target of the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2).

In this study, we aim to find antagonists that may inhibit the activity of the three major viral targets: SARS-CoV-2 3-chymotrypsin-like protease (6LU7), SARS-CoV-2 spike protein (6VYB), and a host target human angiotensin-converting enzyme 2 (ACE2) receptor (1R42), which is the entry point for the viral encounter, were studied with the prospects of identifying significant drug candidate(s) against COVID-19 infection.

Blocking of human angiotensin-converting enzyme 2 (ACE-2) receptor, the binding site of SARS-CoV-2 spike protein, an effective strategy to discover a drug for COVID-19.

With the spike-receptor binding domain (RBD) of SARS-CoV-2 being responsible for binding to human angiotensin-converting enzyme 2 receptor (hACE2), ACE2 is identified as the receptor for the entry and viral infection of SARS-CoV-2.

In the search for inhibitors of COVID-19, we have targeted the interaction between the human angiotensin-converting enzyme 2 (ACE2) receptor and the spike receptor binding domain (S1-RBD) of SARS-CoV-2.

Using in vitro approaches, we investigated the role of a pomegranate peel extract (PPE) in attenuating the interaction between the SARS-CoV-2 Spike glycoprotein and the human angiotensin-converting enzyme 2 receptor, and on the activity of the virus 3CL protease.

Selected molecules were subjected to virtual screening against: (i) human angiotensin-converting enzyme 2 receptor binding domain (hACE-2) which serves as an anchor for virus attachment and entry, (ii) SARS-CoV-2 RNA dependent RNA polymerase (RdRp) responsible for viral RNA replication, and (iii) SARS-CoV-2 main protease (M-Pro) needed for viral polyprotein slab proteolytic processing.

Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a well-known model of SARS-CoV-2 infection.

Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2).

Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells.

Another objective is to analyze the effects of binding Dex and Boc drugs on the interactions of viral spike protein to human angiotensin-converting enzyme 2 (hACE2).

The SARS-CoV-2 receptor-binding spike domain associates itself with human angiotensin-converting enzyme 2 (ACE-2) receptors.

ABSTRACT The nature of intermolecular interactions between the SARS-CoV-2 receptor binding domain (RBD) and its receptor, human angiotensin-converting enzyme 2 (hACE2) has been investigated by Langevin simulations to provides clarity from a dynamic and energetic point of view.

demonstrated the inhibitory activities of curcumin and folic acid, along with those of the known human serine protease inhibitors such as nafamostat and camostat, on human transmembrane protease 2 (TMPRSS2) protein, which is essential for priming spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in association with human angiotensin-converting enzyme 2 (ACE2) surface receptor to facilitate viral invasion into host human cell through ACE2 receptor [1].

In this study, 106 bioactive terpenoids from African medicinal plants were screened through molecular docking analysis against human angiotensin-converting enzyme 2 (hACE2), human transmembrane protease serine 2 (TMPRSS2) and the S proteins of SARS-CoV-2, SARS-CoV and MERS-CoV.

Coronavirus disease 2019 (COVID-19) may be a world pandemic malady caused by the SARS-COV-2 virus surface spike macromolecule binding to the human angiotensin-converting catalyst 2 (ACE2) receptor, that is expressed within the respiratory organ (type two alveolar cells), heart, internal organ epithelial tissue, vascular epithelial tissue, and kidneys, providing a mechanism for multi-organ pathology.

The recent outbreak of the highly contagious coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 has created a global health crisis with socioeconomic impacts Although, recently, vaccines have been approved for the prevention of COVID-19, there is still an urgent need for the discovery of more efficacious and safer drugs especially from natural sources In this study, a number of quinoline and quinazoline alkaloids with antiviral and/or antimalarial activity were virtually screened against three potential targets for the development of drugs against COVID-19 Among seventy-one tested compounds, twenty-three were selected for molecular docking based on their pharmacokinetic and toxicity profiles The results identified a number of potential inhibitors Three of them, namely, norquinadoline A, deoxytryptoquivaline, and deoxynortryptoquivaline, showed strong binding to the three targets, SARS-CoV-2 main protease, spike glycoprotein, and human angiotensin-converting enzyme 2 These alkaloids therefore have promise for being further investigated as possible multitarget drugs against COVID-19 [ABSTRACT FROM AUTHOR] Copyright of Journal of Chemistry is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all s ).

Molecular docking study was performed to elucidate the binding ability of SVS1 and SVS2 with SARS-CoV-2 main protease and human angiotensin-converting enzyme-2 (ACE-2) molecular targets.

Docking calculation confirmed the obtained DFT result as evident from the different binding sites of both drugs to the SARS-CoV-2 main protease and human angiotensin-converting enzyme 2 (ACE2) proteins.

The SARS-CoV-2 virus infects the host human cells through its surface receptors human angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2).

SARS-CoV-2 infection is caused by binding of the viral surface spike (S) protein to the human angiotensin-converting enzyme 2 (ACE2), followed by the activation of the S protein by transmembrane protease serine 2 (TMPRSS2).

SARS-CoV-2 infection is controlled by the opening of the spike protein receptor binding domain (RBD), which transitions from a glycan-shielded ‘down’ to an exposed ‘up’ state to bind the human angiotensin-converting enzyme 2 receptor and infect cells.