A novel biparatopic antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provides a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain (NTD) of the viral S glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain (RBD) of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic virus infection in a standard assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.

Evaluation Of Glove Integrity After Multiple Washes With Disinfectant

Background: In an academic setting due to financialconstrain, it is not uncommon during non-surgicalprocedures dental students and clinical supervisorswash their gloved hands with disinfectants in betweenpatients or when touching on non-contaminatedobjects. Whether this practice could cause anydeterioration of the glove and expose clinicians andpatients to infectious micro-organisms was a concern.Aim: The aim of this study was to investigate the effectof multiple washes of gloved hands with a disinfectanton the integrity of the gloves. Methods: Three brandsof commonly used gloves in a dental school weretested for leaks after multiple washes with adisinfectant. Thirty pairs of each type of gloves weresubjected to 0, 1, 5, 10, 20 and 30 washes with adisinfectant solution at a 5-minute interval betweeneach wash. After each washing cycle, the gloves werefilled with 1L of water and hanged for 2 minutes toobserve any signs of water leaks. Results: The resultsshowed that the type of gloves and number of washeswere significantly associated with the leakage rates(p<0.001). Washing of gloves for more than 5 timeswere at least 6 times higher to suffer from leakage(OR=6.23, 95% CI=2.14–18.08). Powdered gloves werealmost 13 times higher to leak in all washes(OR=12.78, 95% CI= 4.40–37.14) and were almost 25times more likely to leak when washed for more than5 times (OR = 24.92, 95% CI = 5.79 – 107.21) whencompared to the non-powdered gloves. Conclusion:The practice of washing gloved hands with adisinfectant deteriorates the integrity of the gloves.

A non-invasive protocol for the determination of lumbar spine mobility.

OBJECTIVE: This article presents a non-invasive protocol for the determination of lumbar spine mobility and compares intersegmental lumbar spinal mobility data from 45 subjects using both radiographic (invasive) and videographic (non-invasive) techniques. DESIGN: Non-linear mathematical models were developed to transfer skin marker coordinates into corresponding vertebral body positions. BACKGROUND: To relate skin surface motion with that of the underlying vertebrae and to enhance the reliability of using the non-invasive technique relied on a model of transformation. METHODS: This set of models was developed by taking the L(4) skinfold, the L(1)-S(1) skin distraction, and the non-linear difference between the lumbar spinal profile and the skin profile into consideration. Based on the digitized and model transformed data, the intersegmental joint angles (ISA) and intersegmental joint mobilities (ISM) were calculated and compared. RESULTS: In this study the non-invasive and invasive coordinate differences ranged from 0.485 to 1.099 cm; the mean ISA differences ranged from 0.29 to 2.08 degrees the mean ISM differences ranged from 0.62 to 1.88 degrees. CONCLUSIONS: With these small differences, the quality of the non-invasive protocol and the application of the transformation model were justified sufficient.

Predictive model of intersegmental mobility of lumbar spine in the sagittal plane from skin markers.

This article describes a sagittal motion model that transforms skin marker coordinates into corresponding vertebral body coordinates. Coordinate data were obtained from 45 subjects with radiopaque skin markers over the vertebral spinous processes. Data of 30 subjects were used for model development while data of the other Fifteen subjects were used for model validation. The subjects were subjected to lateral spinal radiographs in positions of neutral, flexion, and extension. The model was developed by taking the non-linear difference between lumbar spinal profile and skin profile, the L(4) skin-fold, and the difference of L(1)-S(1) skin distraction into consideration. Regression analysis shows high coefficients of determination (range, 62.43-99.86%; mean, 86.41%) in comparing the estimated position data with the actual data in all vertebral body positions. Based on the estimated coordinates, both the intersegmental joint angles and intersegmental joint mobilities were calculated. The result of this study using the non-invasive protocol and the transformation matrices demonstrated that the intersegmental sagittal motion of lumbar spine can be obtained with error ranged from 0.05 to 0.56 degrees.