Question

The molecular target, a protein that allows entry of the novel coronavirus into infected cells, has been identified. Describe in at least three paragraphs the biological function of the target of the novel coronavirus, in which types of human cells is this target found and which could be the relationship between this receptor and the mechanism of coronavirus disease. Suggest how this information could be utilized to develop a new antiviral drug against the novel coronavirus.

Answer 1

The molecular target , a protein that allows entry of novel coronavirus into infected cell is 'S' or Spike protein.

The CoVs are widely distributed in nature and their zoonotic transmissions into human populations can cause epidemic disease. After entering into respiratory or gastrointestinal tracts, these viruses establish themselves by entering and infecting lumenal macrophages and epithelial cells. The cell entry programs for these viruses are orchestrated by the viral spike (S) proteins that bind cellular receptors and also mediate virus-cell membrane fusions.

The spike protein (S protein) of SARS-CoV has pivotal roles in viral infection and pathogenesis. S1 recognizes and binds to host receptors, and subsequent conformational changes in S2 facilitate fusion between the viral envelope and the host cell membrane.

receptor for this coronavirus is abundantly expressed in certain progenitor cells. These cells normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs.

The spike (S) protein of coronaviruses facilitates viral entry into target cells. Entry depends on binding of the surface unit, S1, of the S protein to a cellular receptor, which facilitates viral attachment to the surface of target cells. In addition, entry requires S protein priming by cellular proteases, which entails S protein cleavage at the S1/S2 and the S2’ site and allows fusion of viral
and cellular membranes, a process driven by the S2 subunit . SARS-S engages angiotensin-converting enzyme 2 .(ACE2) as the entry receptor and employs the
cellular serine protease TMPRSS2 for S protein priming
The SARS-S/ACE2 interface has been elucidated at the atomic level, and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility. SARS-S und SARS-2-S share 76% amino acid iden-
tity. However, it is unknown whether SARS-2-S like SARS-S employs ACE2 and TMPRSS2 for host cell entry.

The present study provides evidence that host cell entry of SARS-CoV-2 depends on the SARS-CoV receptor ACE2 and can be blocked by a clinically proven inhibitor of the cellular serine protease TMPRSS2, which is employed by SARS-CoV-2 for S protein priming. Moreover, it suggests that antibody responses raised against SARS-CoV could at least partially protect against SARS-CoV-2 infection. These results have important implications for
our understanding of SARS-CoV-2 transmissibility and pathogenesis and reveal a target for therapeutic intervention. convalescent SARS patients exhibit a neutralizing antibody response that can be detected even 24 months after infection and that is largely directed against the S protein.
Moreover, experimental SARS vaccines, including recombinant S protein and inactivated virus , induce neutralizing antibody responses. Although confir-
mation with infectious virus is pending, our results indicate that neutralizing antibody responses raised against SARS-S couldNoffer some protection against SARS-CoV-2 infection, which may have implicationsimplications for outbreak control.