The current COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. The virus causes severe respiratory symptoms which manifest disproportionately in the elderly. Currently, there are over 6.5 million cases and 380,000 deaths reported. Given the current severity of the outbreak, there is a great need for antiviral therapies and vaccines to treat and prevent COVID-19. In this review, we provide an overview of SARS-CoV-2 and discuss the emerging therapies and vaccines that show promise in combating COVID-19. We also highlight potential viral targets that could be exploited by researchers and drug manufacturers.

Purpose: To determine the effect of a microinterventional lens prefragmentation wire loop device (miLOOP^®; Carl Zeiss Meditec AG, Oberkochen, Germany), on adverse events (AEs), cumulative dispersed energy (CDE), and vision outcomes when used before phacoemulsification of high-grade mature cataracts. Setting: Three ambulatory surgical centers in the Peoria, IL region. Design: Retrospective comparative consecutive case series; single-surgeon. Methods: Patient outcomes were compared before and after introduction of miLOOP-assisted lens fragmentation prior to phacoemulsification during cataract surgeries performed 2016‒2020. The primary outcome was intraoperative AE rate/type. Secondary outcomes included ultrasound cumulative dispersed energy (CDE) administered during phacoemulsification, postoperative AEs, and best-corrected visual acuity (BCVA). Results: Data from 765 subjects (mean age 72.9 years; 1025 eyes) comprised 524 conventional lens disassembly (Control) eyes and 501 Device eyes. One hundred percent of the cataracts in both groups were advanced WHO Grade 3+ nuclei. Significantly fewer intraoperative AEs occurred in the Device group versus Controls (2.2% and 6.3% of eyes, respectively; p=0.0011). Postoperative AE rates were comparable between groups (Controls=2.9%, Device=3.5%). Mean CDE from ultrasound was significantly reduced by 21% when the microfilament loop device was used for nuclear disassembly (9.6± 5.2 CDE units) versus Controls (11.6± 6.4 CDE units; p< 0.0001). Median postoperative BCVA was 20/25 Snellen (0.091 logMAR) in both groups. More than 70% of both Control and Device eyes had postoperative BCVA better than 20/30 Snellen. Conclusion: Microinterventional lens fragmentation was associated with lower ultrasound energy use and improved intraoperative safety than traditional unassisted surgery of advanced high-grade cataracts, while maintaining similarly acceptable postoperative complication rates and BCVA functional outcomes.

Herpes simplex virus type-1 (HSV-1) exploits several host factors to enhance its replication and release from infected cells. It induces the production of host enzyme heparanase (HPSE) to aid in egress. While the mechanism by which HPSE assists in viral release is well-characterized, other host factors that are recruited along with HPSE for viral release are less well understood. In this study, we identify cyclic-AMP-responsive element-binding protein3 (CREB3) as a key player in HPSE-facilitated HSV-1 egress. When CREB3 is transiently upregulated in human corneal epithelial cells, HSV-1 release from the infected cells is correspondingly enhanced. This activity is linked to HPSE expression such that HPSE-transfected corneal epithelial (HCE) cells more highly express CREB3 than wild-type cells while the cells knocked out for HPSE show very little CREB3 expression. CREB3-transfected HCE cells showed significantly higher export of HPSE upon infection than wild-type cells. Our data suggests that coat protein complex II (COPII), which mediates HPSE trafficking, is also upregulated via a CREB3-dependent pathway during HSV-1 infection. Finally, the co-transfection of CREB3 and HPSE in HCE cells shows the highest viral release compared to either treatment alone, establishing CREB3 as a key player in HPSE-facilitated HSV-1 egress.

Plasma membranes host a plethora of proteins and glycans on their outer surface that are exploited by viruses to enter the cells. In this study, we have utilized this property to limit a viral infection using plasma membrane-derived vesicles. We show that plasma membrane-derived liposomes are prophylactically and therapeutically competent at preventing herpes simplex virus type-1 (HSV-1) infection. Plasma membrane liposomes derived from human corneal epithelial (HCE) cells, which are natural targets of HSV-1 infection, as well as Vero and Chinese hamster ovary (CHO) cells were used in this study. Our study clearly demonstrates that HCE and Vero-derived cellular liposomes, which express the viral entry-specific cell surface protein receptors, exhibit robust antiviral activity especially when compared to CHO-derived liposomes, which lack the relevant HSV-1 entry receptors. Further experimentation of the plasma membrane-derived liposomes with HSV type-2 (HSV-2) and pseudorabies virus yielded similar results, indicating strong potential for the employment of these liposomes to study viral entry mechanisms in a cell free-environment.

To validate a custom FIJI (ImageJ) program for more reproducible, faster curvilinear periorbital measurements, as compared with 2 custom artificial intelligence–based tools. Combined technical validation and method comparison study. Front-facing photographs of 45 cleft palate syndromic patients. A FIJI (ImageJ)-based macro script tool, OrbitJ (semiautomated), was developed, requiring 15 user input steps to generate 38 measurements per photo. The user outlines the irises to set image scale and then selects points along the lid margins and brow lines. Linear interpolation and fourth-degree polynomial fit lines were used to generate periorbital measurements. This tool was compared against our previously developed deep learning algorithm for periorbital measurements, OrbitMap (automated), another open-source algorithm PeriOrbitAI (automated), and against manual measurements. Four human graders measured 45 photos once both manually and with OrbitJ. Intrarater and interrater measurements were performed with 10 photos manually, 3 in triplicate manually and 5 in triplicate with OrbitJ. Fourteen manual measurements were performed: time per image, iris diameter, margin reflex distance (MRD) 1 and 2, inferior scleral show (ISS), medial, central, and lateral brow height, canthal tilt, vertical dystopia, interpupillary distance, and inner and outer canthal distance (OCD). The mean absolute error, reliability, bias, and Pearson correlation of periorbital measurements. Analysis was successful in all 45 images for all methods except PeriOrbitAI, which failed on 6 images. For manual and semiautomated intra- and interrater measurements, reliability was considered moderate or better (intraclass correlation coefficient [ICC] >0.5) for all measurements excluding elapsed time. Manual interrater mean absolute error was 0.8) between all OrbitJ and manual measurements. Comparing OrbitMap to manual measurements, ICC and Pearson correlation coefficient were >0.5 except for ISS, borderline for OCD (ICC = 0.51). Reliability between PeriOrbitAI and manual measurements was low (ICC <0.5) except for MRD2 and OCD, and correlation was moderate (Pearson correlation coefficient = 0.49–0.75). The mean analysis time per image was 13.4 ± 4 minutes (manual measurements), 5.4 ± 1.9 minutes (semiautomated OrbitJ), 10.71 ± 1.65 seconds (automated PeriOrbitAI), and 1.45 ± 0.15 seconds (automated OrbitMap) (P < 0.001). Compared with manual measurements, all semiautomated OrbitJ measurements and most automated OrbitMap measurements were reliable. Notably, only 2 PeriOrbitAI measurements were reliable. All methods demonstrated significant time savings over manual measurements. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.