Best matches for Zinc , coronavirus:
Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials.
Warnes SL et al. mBio.
(2015)
Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion.
Phillips JM et al. J Virol.
(2017)Abstract
The coronavirus
(CoV) S protein requires cleavage by host cell proteases to mediate
virus-cell and cell-cell fusion. Many strains of the murine coronavirus
mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue
tropisms despite using a common receptor, suggesting that they employ
different cellular proteases for fusion. In support of this hypothesis,
we found that inhibition of endosomal acidification only modestly
decreased entry, and overexpression of the cell surface protease TMPRSS2
greatly enhanced entry, of the highly neurovirulent MHV strain JHM.SD
relative to their effects on the reference strain, A59. However, TMPRSS2
overexpression decreased MHV structural protein expression, release of
infectious particles, and syncytium formation, and endogenous serine
protease activity did not contribute greatly to infection. We therefore
investigated the importance of other classes of cellular proteases and
found that inhibition of matrix metalloproteinase (MMP)- and a
disintegrin and metalloprotease (ADAM)-family zinc
metalloproteases markedly decreased both entry and cell-cell fusion.
Suppression of virus by metalloprotease inhibition varied among tested
cell lines and MHV S proteins, suggesting a role for metalloprotease use
in strain-dependent tropism. We conclude that zinc metalloproteases must be considered potential contributors to coronavirus fusion.
IMPORTANCE The family Coronaviridae includes viruses that cause two emerging diseases of humans, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as a number of important animal pathogens. Because coronaviruses depend on host protease-mediated cleavage of their S proteins for entry, a number of protease inhibitors have been proposed as antiviral agents. However, it is unclear which proteases mediate in vivo infection. For example, SARS-CoV infection of cultured cells depends on endosomal acid pH-dependent proteases rather than on the cell surface acid pH-independent serine protease TMPRSS2, but Zhou et al. (Antiviral Res 116:76-84, 2015, doi:10.1016/j.antiviral.2015.01.011) found that a serine protease inhibitor was more protective than a cathepsin inhibitor in SARS-CoV-infected mice. This paper explores the contributions of endosomal acidification and various proteases to coronavirus infection and identifies an unexpected class of proteases, the matrix metalloproteinase and ADAM families, as potential targets for anticoronavirus therapy.
IMPORTANCE The family Coronaviridae includes viruses that cause two emerging diseases of humans, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as a number of important animal pathogens. Because coronaviruses depend on host protease-mediated cleavage of their S proteins for entry, a number of protease inhibitors have been proposed as antiviral agents. However, it is unclear which proteases mediate in vivo infection. For example, SARS-CoV infection of cultured cells depends on endosomal acid pH-dependent proteases rather than on the cell surface acid pH-independent serine protease TMPRSS2, but Zhou et al. (Antiviral Res 116:76-84, 2015, doi:10.1016/j.antiviral.2015.01.011) found that a serine protease inhibitor was more protective than a cathepsin inhibitor in SARS-CoV-infected mice. This paper explores the contributions of endosomal acidification and various proteases to coronavirus infection and identifies an unexpected class of proteases, the matrix metalloproteinase and ADAM families, as potential targets for anticoronavirus therapy.
Copyright © 2017 American Society for Microbiology.
Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein.
Lei J et al. Antiviral Res.
(2018)The multi-domain non-structural protein 3 (Nsp3) is the largest protein encoded by the coronavirus
(CoV) genome, with an average molecular mass of about 200 kD. Nsp3 is
an essential component of the replication/transcription complex. It
comprises various domains, the organization of which differs between CoV
genera, due to duplication or absence of some domains. However, eight
domains of Nsp3 exist in all known CoVs:
- the ubiquitin-like domain 1 (Ubl1),
- the Glu-rich acidic domain (also called "hypervariable region"),
- a macrodomain (also named "X domain"),
- the ubiquitin-like domain 2 (Ubl2),
- the papain-like protease 2 (PL2pro),
- the Nsp3 ectodomain (3Ecto, also called "zinc-finger domain"),
- as well as the domains Y1 and
- CoV-Y of unknown functions.
In
addition, the two transmembrane regions, TM1 and TM2, exist in all CoVs.
The three-dimensional structures of domains in the N-terminal two
thirds of Nsp3 have been investigated by X-ray crystallography and/or
nuclear magnetic resonance (NMR) spectroscopy since the outbreaks of
Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003 as well as Middle-East Respiratory Syndrome coronavirus (MERS-CoV) in 2012. In this review, the structures and functions of these domains of Nsp3 are discussed in depth.
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