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Drug: Isotretinoin plus TamoxifenWiki

Developed by Shray Alag
Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (3)


Name (Synonyms) Correlation
drug2315 Standard care delivered in the isolation hospitals. Wiki 1.00
drug134 Aerosolized Isotretinoin plus Tamoxifen Wiki 1.00
drug2547 Tramadol Wiki 1.00

Correlated MeSH Terms (2)


Name (Synonyms) Correlation
D045169 Severe Acute Respiratory Syndrome NIH 0.05
D018352 Coronavirus Infections NIH 0.04

Correlated HPO Terms (0)


Name (Synonyms) Correlation

There is one clinical trial.

Clinical Trials


1 Combination Therapy With Isotretinoin and Tamoxifen Expected to Provide Complete Protection Against Severe Acute Respiratory Syndrome Coronavirus

Combination Therapy with Isotretinoin and Tamoxifen expected to provide Complete Protection against Severe Acute Respiratory Syndrome Coronavirus Abstract: The COVID-19 pandemic caused by SARS-COV-2 has infected over 2,000,000 people causing over 150,000 deaths.Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and for which there are currently no approved treatments.The principal investigator reported according to previous research data that combination therapy with Isotretinoin and tamoxifen expected to provide Complete Protection against Severe Acute Respiratory Syndrome Coronavirus, 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. A study demonestrated 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, 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) Moreover, another study 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. As Investigators discussed before in their previous clinical trial (NCT04353180) that Isotretinoin is the strongest down-regulator of ACE2. and the principal investigator expects that Isotretinoin can inhibit or downrgulat ACE2 by direct interaction and binding with the transmembrane ACE2, Suggesting its therapeutic potential in preventing the entry of COVID 2019 to the host cell. The second combined drug is tamoxifen, A study demonstrated that tamoxifen causes redistribution of weak base chemotherapeutics from acidic organelles to the nucleus in drug-resistant cells. Agents that disrupt organelle acidification (e.g., monensin, bafilomycin A1) cause a similar redistribution. Measurement of cellular pH in several cell lines reveals that tamoxifen inhibits acidification of endosomes and lysosomes without affecting cytoplasmic pH, Tamoxifen decreased the rate of vesicular transport though the recycling and secretory pathways. Organellar acidification is required for many cellular functions, and its disruption could account for many of the side effects of tamoxifen. A sudy demonstrated that the phagocytosis is inhabited by tamoxifen and chloroquine in retinal epithelial cells and Also, a study demonstrated that Tamoxifen have weak base property and increase endolysosomal pH and alter endosomal dynamics. Importantly, TAM treatment enhanced survival of mice injected with a lethal dose of STx1 or STx2,The protective effect was independent of estrogen receptors but dependent on the weak base property of TAM, which allowed TAM to increase endolysosomal pH and alter endosomal dynamics. A study demonstrated that Tamoxifen have antimalarial effect via treating mice infected with P. berghei, which show lower levels of parasitaemia and do not develop signs of cerebral malaria, Tamoxifen is found to prevent lung fibrosis and reduce serum TGFβ-1 levels. A study Reported that Tamoxifen have endosomal and lysosomal cysteine proteases inhibitory effect better than chloroquine , Cathepsins are endosomal and lysosomal cysteine proteases that play important roles in protein degradation in various cellular processes including both the endocytic pathway and autophagy. The role of cathepsins in viral infection was first identified by Huang et al and they found that one cysteine proteases inhibitor E64d and a specific cathepsin L inhibitor Z-FY(t-Bu)-DMK are able to block the SARS-CoV infection. A study demonestrated that Cathepsin D was more sensitive to tamoxifen than to chloroquine. Tamoxifen exposures decreased the cathepsin D activity at less than 10 pM concentrations. The effect of chloroquine started at concentration of 15 pM, Finally, the principal investigator expects strong inhibition of COVID-19 by this combination therapy. Keywords: COVID 2019 , Isotretinoin , Tamoxofin, ACE2,.Endosomal and Lysosomal pH.

NCT04389580 COVID-19 Drug: Drug: Isotretinoin plus Tamoxifen Drug: Aerosolized Isotretinoin plus Tamoxifen
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Proportion of lung injury score decreased or increased after treatment

Measure: lung injury score

Time: at 7 days

Secondary Outcomes

Description: lymphocyte counts

Measure: Absolute lymphocyte counts

Time: at day 7 and 14

Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

Time: at day 7 and 14

Description: Serum level of COVID19 RNA

Measure: Serum level of COVID19 RNA

Time: at day 7 and 14

Measure: All cause mortality rate

Time: at day 7 and 14

Measure: Ventilation free days

Time: at 14 days

Measure: ICU free days

Time: at 14 days

Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample

Measure: d-dimers

Time: at 3-5 days

Description: (if pos. at baseline)

Measure: Time to first negative SARS-CoV-2 PCR in NP swap

Time: 14 days


No related HPO nodes (Using clinical trials)