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SARS-CoV-2 proteins

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    O-β-GlcNAcylation, Chloroquine and 2-Hydroxybenzohydrazine May Hamper SARS-CoV-2 entry to Human via Inhibition of ACE2 HGNC Phosphorylation at Ser787 but Also Induce Disruption of Virus- ACE2 HGNC Binding

    Authors: Waqar Ahmad; Khadija Shabbiri; Nazarul Islam

    id:10.20944/preprints202004.0390.v1 Date: 2020-04-22 Source: Preprints.org

    The novel coronavirus COVID- 19 disease is extremely contagious and has been spread worldwide. First COVID-19 MESHD case was identified in December, 2019 and within three months, more than one million affected cases and over 65,000 deaths have been reported. SARS-coronavirus MESHD 2 (SARS-CoV-2) also known as 2019-nCoV is a causative agent of COVID-19 MESHD disease and belongs to the SARS CoV ( Severe Acute Respiratory Syndrome corona virus MESHD) family. The SARS-CoV-2 enters the human body by binding its viral surface spike protein PROTEIN with the host angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC) receptors and cause infection. To prevent the virus entry and its transmission in the human body, we focused on the two domains of ACE2 HGNC: i) the N-terminal extracellular binding domain (18-740 residues) reported for coronavirus spike interaction, and ii) the C-terminal cytoplasmic region (762-805 residues) to prevent the virus transmission. Therefore, we proposed: i) inhibition of receptor binding domain (RBD) of SARS-CoV-2 and human ACE2 HGNC protein may prevent the virus entry to the host and ii) inhibition of phosphorylation at Ser-787 of ACE2 HGNC protein may prevent the transmission of the virus in the COVID-19 MESHD patients. In the past, the critical role of Ser 787 in human ACE2 HGNC protein has been experimentally verified in SARS-CoV transmission, that upon binding to the receptor, SARS- CoV induces CKII HGNC- mediated phosphorylation of ACE2 HGNC at Ser-787 that in-turn facilitate virus entry to host cells, followed by replication and activation of ACE2 HGNC, initiates downstream signaling leading to lung fibrosis MESHD. Therefore, in this study, we have suggested post-translational modification (PTM) O-β-GlcNAcylation, and two compounds Chloroquine and 2-hydroxybenzohydrazine might share the common pathways to prevent the COVID-19 MESHD infection in human. The addition of O-β-GlcNAcylation at same or neighboring Ser/ Thr residues results in phosphorylation inhibition and a change in protein structural and functional confirmations. Thereby, using neural networking methods, we have identified Ser/ Thr residues in ACE2 HGNC that are potential sites for phosphorylation and / or O-β-GlcNAcylation. Molecular docking showed that UDP-GlcNAc has more binding affinity with Ser-787 than the phosphoryl group. Moreover, chloroquine and 2-hydroxybenzohydrazine also showed great potential to bind at Ser-787 that may result in inhibition of Ser-787 phosphorylation and downstream signaling. Furthermore, O-β-GlcNAcylation, chloroquine and 2-hydroxybenzohydrazine showed their high affinity at ACE2 HGNC-SARS-CoV-2receptor binding domain that may prevent the entry of SARS-CoV-2 into human body. In conclusion, inhibition of human ACE2 HGNC phosphorylation at Ser-787 and ACE2 HGNC-SARS-CoV-2 binding domain could be promising targets against SARS-CoV-2 infection MESHD.

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MeSH Disease
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