Designing a humanized immunotoxin based on DELTA-stichotoxin-Hmg2a toxin: an in silico study.

Breast cancer remains the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women. HER2 positive subtype includes 15-20% of breast cancer cases. This receptor could be an appropriate mark for targeting breast cancer cells. Immunotherapy methods compared to current cancer treatment methods have the lowest side effects. DELTA-stichotoxin-Hmg2a is isolated from the sea anemone and kills cells through pore formation. In the current study, we designed and evaluated an immunotoxin composed of pertuzumab and DELTA-stichotoxin-Hmg2a-derived scFv by bioinformatics tools. The designed immunotoxin was constructed using the amino acid sequences. Then, secondary structure and physico-chemical features were studied, and the tertiary structure of the immunotoxin was built according to the homology modeling methods. The validation and allergenicity of the model were assessed. The immunotoxin and receptor were docked and molecular dynamics simulation indicated the construct stability. The analysis results indicated that the construct is a stable protein that could have a natural-like structure and would not be an allergen, so this immunotoxin could effectively target HER2 receptors. Therefore, our designed immunotoxin could be an appropriate immunotoxin against HER2-positive breast cancer and could be a challenging topic for future in vitro and in vivo studies.

The identification of novel inhibitors of human angiotensin-converting enzyme 2 and main protease of Sars-Cov-2: A combination of in silico methods for treatment of COVID-19.

The angiotensin-converting enzyme 2 (ACE2) and main protease (MPro), are the putative drug candidates for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we performed 3D-QSAR pharmacophore modeling and screened 1,264,479 ligands gathered from Pubchem and Zinc databases. Following the calculation of the ADMET properties, molecular docking was carried out. Moreover, the de novo ligand design was performed. MD simulation was then applied to survey the behavior of the ligand-protein complexes. Furthermore, MMPBSA has utilized to re-estimate the binding affinities. Then, a free energy landscape was used to find the most stable conformation of the complexes. Finally, the hybrid QM-MM method was carried out for the precise calculation of the energies. The Hypo1 pharmacophore model was selected as the best model. Our docking results indicate that the compounds ZINC12562757 and 112,260,215 were the best potential inhibitors of the ACE2 and MPro, respectively. Furthermore, the Evo_1 compound enjoys the highest docking energy among the designed de novo ligands. Results of RMSD, RMSF, H-bond, and DSSP analyses have demonstrated that the lead compounds preserve the stability of the complexes' conformation during the MD simulation. MMPBSA data confirmed the molecular docking results. The results of QM-MM showed that Evo_1 has a stronger potential for specific inhibition of MPro, as compared to the 112,260,215 compound.

Undiagnosed interrupted aortic arch in a 59-year-old male patient with severe aortic valve stenosis: A case report and literature review.

BACKGROUND: Interrupted aortic arch (IAA) is defined by a lack of the luminal continuity between the ascending and descending thoracic aorta. It is a rare, severe congenital heart defect which without surgery is associated with high mortality in the neonatal period. The aims of this study were to present a case with IAA who was alive until the age of 59 years without any surgical intervention and to review the literatures that have presented IAA cases. CASE REPORT: The patient was admitted with respiratory distress and pulmonary edema. Echocardiography showed the sever stenosis in aortic valve and sever left ventricular dysfunction. Cardiac catheterization and angiography confirmed interrupted aorta (type A). The descending thoracic aorta was supplied by extensive collateral vessels from the vertebrobasilar system down to the posterior chest wall and the spine. Surgical correction including coronary artery bypass graft and aortic valve replacement and repair of interruption of the aorta was performed. Three weeks later the patient was died due to uncontrollable gastrointestinal bleeding and hospital acquired pneumonia. We described diagnosis and management of our case. CONCLUSION: This case was very interesting for us, because the patient had not been diagnosed until the recent presentation. Similar cases with this diagnosis do not reach adulthood, but our patient was alive up to 59 years of age.

Diagnostic dilemma: Saccular aneurysm or pseudoaneurysm of the ascending aorta with dissection above level of leaflets.

BACKGROUND: In true aneurysm, the wall of aneurysm is composed of the normal histological components of aorta. A false aneurysm (pseudoaneurysm) represents a rupture which does not contain the normal histological components of aorta. It is a fibrous peel that has formed from a small perforation of aorta. We describe an unusual presentation that has signs which some of them are only manifested in true aneurysm and some others only in pseudoaneurysm. CASE REPORT: An 85-year-old man underwent elective coronary angiography for chest pain work-up. Our evaluation by invasive angiography and CT angiography showed aortic dissection. In surgery we found that dissection flap was composed of some parts of intima and media layers. These signs leaded to confusing symptoms. Localized bulging of ascending aorta had continued to brachiocephalic artery (transverse arch involvement). Dissection flap was composed of some part of intima and media layers. It was a strange case, it was not solely a perivascular hematoma and it did not have all three layers of aorta wall. Partial aorta replacement was performed. The operation and recovery was uneventful. CONCLUSION: This unusual presentation of disease has not been mentioned in literatures. Our experience can help to manage similar cases. This case was the first unusual presentation of its type.