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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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SARS-CoV-2, Early Entry Events.

James P Chambers1, Jieh Yu1, James J Valdes1,2

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|December 10, 2020
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Summary
This summary is machine-generated.

SARS-CoV-2 enters host cells through a complex process involving spike protein attachment to ACE2 receptors and proteolytic cleavage. This cleavage, dependent on furin and TMPRSS2 proteases, is crucial for viral membrane fusion and infection.

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Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Viruses are obligate intracellular parasites, with host cell entry being the initial stage of their life cycle.
  • SARS-CoV-2 (COVID-19) utilizes its spike (S) protein to bind to host cell angiotensin-converting-enzyme 2 (ACE2) receptors, initiating infection.
  • This entry involves complex steps: attachment, S protein proteolytic processing at S1/S2 and S2' sites, and membrane fusion.

Purpose of the Study:

  • To elucidate the intricate mechanisms of SARS-CoV-2 host cell entry.
  • To identify the specific proteases involved in the proteolytic processing of the SARS-CoV-2 spike protein.
  • To understand the role of ACE2 receptor cleavage in viral infectivity and host cell function.

Main Methods:

  • Analysis of viral life cycle and host cell interactions.
  • Investigation of spike protein structure and function, including receptor-binding motif (RBM) interactions.
  • Identification of protease involvement through various cell-based studies (specific proteases not detailed in abstract).

Main Results:

  • SARS-CoV-2 entry requires S protein attachment to ACE2, proteolytic cleavage, and membrane fusion.
  • Spike protein cleavage occurs at S1/S2 and S2' sites, generating fusion-competent elements.
  • Proteolytic cleavage appears to be dependent on the concerted action of furin and transmembrane protease serine 2 (TMPRSS2).
  • ACE2 receptor cleavage adds complexity and may affect its cardiovascular and immune functions.

Conclusions:

  • The SARS-CoV-2 entry mechanism is a multi-step process involving specific protein interactions and enzymatic processing.
  • Furin and TMPRSS2 are key proteases facilitating SARS-CoV-2 spike protein cleavage, essential for viral entry.
  • Alterations in ACE2 receptor function due to cleavage may have broader implications for host health, particularly in cardiovascular and immune systems.