Key words
antiviral drugs - pharmacology - drug research
To the Editor
SARS-CoV-2 infection was first isolated in Wuhan in the end of December 2019, since
then, this β-coronavirus has rapidly spread becoming the most important
public health concern worldwide. Numerous research Centers are working hard to
realize a sure and effective medicine/vaccine as soon as possible, however
the timing for having the availability of a curative/preventive treatments
are unpredictable. Considering the severe health and economic consequences related
with the SARS-CoV-2 pandemic, physicians are testing different antiretroviral and
non-antiretroviral drugs for treating infected patients. Scientific literature
review has shown interesting information about the potential antiretroviral action
of some compounds not conventionally used for the treatment of virosis. Adem and
colleagues in their virtual screening based molecular docking study reported a
potential binding affinity exerted by various bioflavonoids at the active site of
the MPro, the main protease of the SARS-CoV-2 [1]. Potential inhibition properties were studied using the Molegro
Virtual Docker Program and some flavonoids, in particular hesperidin, rutin, and
diosmin showed a better affinity for the MPro than nelfinavir [1]. Hesperidin showed the highest binding
energy at the active site of the MPro with a MoLDock score of −178.5910
(nelfinavir -147.3800) and a HBond of −20.2594 (nelfinavir −6.8731).
Moreover, the hesperidin could bind both Spike protein and ACE2 receptor preventing
the development of the spike-ACE2 complex used by the virus to enter cells [2]. Rutin showed the second strongest binding
energy at the active site of the MPro with a MoLDock score of −176.2740 and
a HBond of −21.2402. Additionally, in preclinical studies the rutin reduced
the level of interleukin 6, a pro-inflammatory cytokine involved in the
"cytokine storm" responsible for some severe infection-related
complications [3]. Diosmin highlighted the
third strongest binding energy at the active site of the MPro with a MoLDock score
of −174.1260 and a HBond of −27.2572. As signaled for the rutin, in
preclinical models the diosmin reduced the level of interleukin 6 as well as the
number of CD4 and CD8 receptors in T cells [4]. Recently, Caly and colleagues reported a potential antiretroviral
activity of the anti-parasitic agent ivermectin against SARS-CoV-2 virus. They
demonstrated a reduction of about 5000-fold of viral RNA in ivermectin-treated cells
compared to control samples after 48 hours treatment. Ivermectin have showd
antiviral effects against HIV, West Nile, Venezuelan equine encephalitis, and
pseudorabies in previous preclinical and clinical studies [5]. Hoffmann and colleagues have further shown
that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease
TMPRSS2 for Spike protein priming [6]. So,
inhibition of the androgen-regulated serine protease TMPRSS2 activity could be a
probable target for antiretroviral treatments. About that, bromhexine, a well
tolerated mucolytic acting as cough suppressant, displayed to be able to inhibit the
TMPRSS2 in a mice model study [7]. SARS-CoV-2
infection is causing thousands of victims worldwide by subjecting healthcare workers
to an unprecedented effort. Despite the absence of clinical evidences regarding some
potential anti-SARS-CoV-2 drugs, preliminar information reported by researchers
suggest anyhow further studies in order to evaluate the clinical effects as well as
the possibility to synthesize derivatives with stronger antiretroviral properties.
Compounds reported in our paper have shown a safety profile for human and a
potential anti-SARS-CoV2 activity.
