Contributors:
Lamia Elgarhy, Sabah El-Gaeish 1, Eman Hamed 2 , Wagdy Fathy2 Department of Dermatology,
Department of Pharmacology1 , Faculty of Medicine, Tanta University, Department of Chest,
Faculty of Medicine, Suez Canal University2.
Abstract:
The COVID-19 pandemic caused by SARS-COV-2 has infected over 2,000,000 people causing over
150,000 deaths. A key host cellular protein required for the virus entry is
angiotensin-converting enzyme 2 (ACE2) whose expression has been demonstrated in many tissues
including alveolar epithelial type II cells in lungs, oral mucosa and intestine, heart,
kidney, endothelium and skin. ACE2-expressing cells can act as home cells and are prone to
SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. (1)
Fang et al. has suggested that patients with hypertension and diabetes mellitus may be at
higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors
(ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously
suggested to increase ACE2 expression. (2) In another study by Sinha et al who analyzed a
publicly available Connectivity Map (CMAP) dataset of pre/post transcriptomic profiles for
drug treatment in cell lines for over 20,000 small molecules, isotretinoin was the strongest
down-regulator of ACE 2 receptors. On the other hand, they found 6 drugs in CMAP that are
currently being investigated in clinical trials for treating COVID-19 (chloroquine,
thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov),
none of which was found to significantly alter ACE2 expression (P>0.1) (3) Moreover, Wu et
al, demonstrated that isotretinoin is a Potential papain like protease (PLpro) inhibitors
which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should
be targeted in COVID-19 treatment by performing target-based virtual ligand screening. (4) In
addition, isotretinoin was reported to increase CD4 counts and markedly decrease viremia in
HIV positive patients suffering from acne vulgaris. (5) Currently, a study is running to
evaluate the effect of isotretinoin on immune activation among HIV-1 infected subjects with
incomplete CD4+ T cell recovery. (6) From this point, we can suggest that patient taking
isotretinoin therapy may be immune against SARS-COV-2 and it can also have a therapeutic
effect by prevention of further progression of the virus. Several potential mechanisms of
action of Chloroquine/Hydroxychloroquine against SARS-CoV-2 have been postulated and they are
actually used in treatment regimens for COVID-19.(7) It was reported that chloroquine
increase the blood level of isotretinoin, so lower doses is required when combined. We assume
to test the efficacy of isotretinoin in treatment of COVID-19 versus combined therapy with
the standard treatment of COVID-19.