Potential Antiviral activity of Pentoxifylline and Caffeine for
COVID-19 treatment
The spike (S) protein of coronaviruses (CoV ) allows viral entry to the
target cells (Hoffmann et al. 2020). CoV
S protein is an essential component in determining the virulence of the
virus, tissue tropism, and host range. The SARS-S protein uses
angiotensin-converting enzyme 2 (ACE 2) as the entry receptor
(Li et al. 2003), and the cellular serine
protease TMPRSS2 carries out the S-protein priming and activation
(Shulla et al. 2011). SARS-S protein of
SARS-CoV and SARS-2-S protein of SARS-CoV-2 share about 76% amino acid
identity. Following the previous results, a recent study showed
compelling evidence that the entry of SARS-CoV-2 also depends on the ACE
2 receptor, and this entry can be blocked by serine protease TMPRSS2
inhibitor (Hoffmann et al. 2020).
Similarly, another study also reported SARS-CoV-2-S protein entry on
293/hACE2 cells is mainly mediated by endocytosis
(Ou et al. 2020). Following its entry,
the virus expresses the genes encoding all structural and accessory
proteins by adopting the genome of their host. The viral nucleocapsids
are assembled in the cytoplasm, enter into the lumen of the endoplasmic
reticulum (Graham and Baric 2010).
Subsequently, virions will be released through the process of
exocytosis. They can infect various cells, including T lymphocytes, as
well as organs like the liver, kidney, and the lower respiratory tract
(Tynell et al. 2016). Therefore, they
can provide potential drug targets, and also antibody raised against
SARS-CoV could at least partly protect against SARS-CoV-2 infection and
both the serine protease TMPRSS2 and the ACE 2 could be a possible
target for therapeutic intervention
(Hoffmann et al. 2020).
Broad-spectrum antiviral drugs such as IFN-alpha, protease inhibitors
like the lopinavir, nucleoside analogs, including ribavirin, and
Neuraminidase inhibitors such as remdesivir can be used as a potential
antiviral treatment for the coronavirus infected patients via
interfering at different stages of the viral replication cycle. However,
there is a lack of enough clinical data and direct evidence in COVID-19
patients are yet to be studied.