Computational screening for potential drug candidates against the SARS-CoV-2 main protease.

Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa M pro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that M pro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 M pro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

Evaluation of human bone around a dental implant retrieved from a subject with osteoporosis.

Osteoporosis is a metabolic bone disease that leads to bone fragility and an increase in the risk of bone fracture. Nowadays, osteoporosis may represent a contraindication or a risk factor for osseointegration; however, this field still is controversial in the literature. This article sought to evaluate the bone-to-implant contact of a loaded implant that had been retrieved (due to prosthetic failure) from a woman with Type 1 osteoporosis. Histologically, the implant was osseointegrated and appeared to be surrounded by healthy bone tissue. The bone-to-implant contact demonstrated a mean of 40.07% (+/- 1.07%). No foreign body reaction was found at the bone-to-implant contact, although epithelial downgrowth was observed at the interface. Data from this case report demonstrate that the peri-implant bone histology is not altered even when a patient has been diagnosed with osteoporosis.

Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations.

STUDY OBJECTIVES: Pulmonary arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia (HHT) can cause hemorrhage, stroke, and cerebral abscess. Therapy consists of transcatheter embolotherapy (TCET) to occlude the PAVMs. Contrast transthoracic echocardiography (TTE) can be used to screen for PAVMs, but little is known about the performance of contrast TTE after TCET has been performed. Our objective was to determine the effect of the successful performance of TCET on the performance of contrast TTE, specifically, in what proportion of patients the findings of contrast TTE normalized or remained positive after the performance of TCET. DESIGN: Retrospective chart review. SETTING: HHT clinic at university teaching hospital. PATIENTS: Patients who have undergone TCET for the treatment of PAVMs. INTERVENTIONS: Patients were screened for PAVMs with a chest radiograph (CXR), oxygen shunt test (OST), and contrast TTE. Pulmonary angiography was recommended for patients with any positive findings on a screening test. PAVMs > or = 3 mm were occluded by TCET. Contrast TTE, OST, and CXR were performed approximately 1 month later. The results of contrast TTE before and after patients underwent TCET were compared. MEASUREMENTS AND RESULTS: Thirty-nine patients underwent contrast TTE prior to undergoing TCET, and 29 patients underwent contrast TTE both prior to and after undergoing TCET. In all patients, TTE findings were positive prior to TCET. All PAVMs with feeding vessels > or = 3 mm were successfully occluded based on completion angiography. After TCET, 48% of patients had no detectable residual PAVMs, and the remainder had small (ie, < 3 mm) residual PAVMs. Of the 29 patients, 90% had positive contrast TTE findings after undergoing TCET. In the subset of patients who had no residual PAVMs on the completion angiography, 80% had positive contrast TTE findings after undergoing TCET. CONCLUSIONS: In most patients, contrast TTE findings remain positive after they undergo TCET, even in patients without residual PAVMs seen on angiography. This may reflect residual PAVMs that are too small to visualize using angiography. These findings have important implications for the follow-up and management of HHT patients.