4.3.2.2. In Vitro Studies
Parallel to in silico studies, in vitro studies, have also
been performed to identify potent phytochemical-based anti-SARS-CoV-2
compounds, however, very few phytochemicals have been considered forin vitro analysis. When Homoharringtonine, a plant alkaloid with
high antiviral properties, was tested in vitro for its
anti-SARS-CoV-2 activity, exhibited SARS-CoV-2 inhibition at an
EC50 of 2.10 uM. In addition, Emetine, an isoquinoline
derivative that is approved for the treatment of amoebiasis, was also
shown to successfully inhibit SARS-CoV-2 at an EC50 of
around 0.5 uM. Taking their observations further, the same study tried
an approach of combinational drug treatment using Remdesivir and
Emetine, and they found that Remdesivir at 6.25 uM and in combination
with Emetine at 0.195 uM exhibited 64.9% inhibition of the viral yield
. Their study opens avenues for further work to be carried out in the
field of combinational therapy using phytoconstituents, which will lead
to better clinical outcomes. Another recent in vitro study was
conducted specifically to evaluate the anti-SARS-CoV-2 activity of
Lycorine, Emetine, and Cephaeline, demonstrated excellent COVID-19
inhibition. However, owing to their biological toxicity, further
research needs to be conducted to modify these compounds to make them
safer for consumption .
Berberine has already been identified to have good antiviral activity
against SARS-CoV-2 through in silico studies, and this is also
supported by in vitro studies carried out on Vero E6 cells. The
study highlights the potent antiviral activity of Berberine at an
EC50 of 9.1 uM, and a continued analysis in infected
epithelial cells also reported good viral inhibition at
EC50 of 10.7 uM. This study also throws light on the
fact Berberine acts on early as well as later stages of COVID-19
infection, and thus represents an excellent candidate for furtherin vivo and clinical studies. Resveratrol, a type of stilbenoid
belonging to polyphenols, with abundant medical benefits, was identified
as a powerful SARS-CoV-2 inhibitor. A recent biological assay performed
on Vero E6 cells demonstrated a reduction in SARS-CoV-2 replication by 3
logs at 25μM, with an EC50 of 4.48 uM. However, the bioavailability of
Resveratrol poses a difficulty, which can be overcome if the drug can be
administered through the nasotracheal route, and further research
followed by clinical trials are required to ascertain the safety and
efficiency of Resveratrol.
A series of in vitro studies performed to test the efficiency of
Glycyrrhizin which is a triterpene saponin, identified it to be a good
inhibitor of Mpro (SARS-CoV2 main viral protease), The antiviral active
levels of the drug were within the range of that tolerated by humans,
indicating that with further in vivo and clinical validation,
Glycyrrhizin could also be one of the potential phytocompound that can
be used to treat COVID-19. An in vitro study reported that EGCG
expressed potent antiviral activity against Nsp15 of SARS-CoV-2, thus
showing that EGCG containing compounds could be excellent inhibitors of
viral replication. The study also suggests various methods of
administration of EGCG in the form of mouthwashes or nasal washes. EGCG
is potent even at very low concentrations. Therefore, this phytocompound
is pointed out as a powerful lead for further investigation. The method
of in vitro evaluation and analysis of the biological activity of
potential drug molecules is shown in Figure 5 .