Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using 177Lu-iPSMA and 177Lu-DOTATOC: Experience after 905 Treatment Doses.

177Lu-iPSMA is a novel radioligand developed at ININ-Mexico with a high affinity for the PSMA protein heavily expressed in cancer cells of approximately 95% of patients with metastatic castration-resistant prostate cancer (mCRPC). 177Lu-DOTATOC is a patent-free radioligand, molecularly recognized by somatostatin receptors (SSTR-2) overexpressed in cancer cells of about 80% of patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET). This translational research aimed to determine the efficacy and safety of 177Lu-iPSMA and 177Lu-DOTATOC developed as GMP pharmaceutical formulations for treating progressive and advanced mCRPC and NET. One hundred and forty-five patients with mCRPC and one hundred and eighty-seven subjects with progressive NET (83% GEP-NET and 17% other NET), treated with 177Lu-iPSMA and 177Lu-DOTATOC, respectively, were evaluated. Patients received a mean dose of 7.4 GBq per administration of 177Lu-iPSMA (range 1-5 administrations; 394 treatment doses) or 177Lu-DOTATOC (range 2-8 administrations; 511 treatment doses) at intervals of 1.5-2.5 months. Efficacy was assessed by SPECT/CT or PET/CT. Results were stratified by primary tumor origin and number of doses administered. Patients with mCRPC showed overall survival (OS) of 21.7 months with decreased radiotracer tumor uptake (SUV) and PSA level in 80% and 73% of patients, respectively. In addition, a significant reduction in pain (numerical scale from 10-7 to 3-1) was observed in 88% of patients with bone metastases between one and two weeks after the second injection. In the GEP-NET population, the median progression-free survival was 34.7 months, with an OS of >44.2 months. The treatments were well tolerated. Only ten patients experienced grade ≥ 3 myelosuppression (3% of all patients). The observed safety profiles and favorable therapeutic responses demonstrated the potential of 177Lu-iPSMA and 177Lu-DOTATOC to improve overall survival and quality of life in patients with progressive and advanced mCRPC and NET.

Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.

Coronaviruses (CoVs) are enveloped and positive-stranded RNA viruses with a large genome (∼ 30kb). CoVs include essential genes, such as the replicase and four genes coding for structural proteins (S, M, N and E), and genes encoding accessory proteins, which are variable in number, sequence and function among different CoVs. Accessory proteins are non-essential for virus replication, but are frequently involved in virus-host interactions associated with virulence. The scientific literature on CoV accessory proteins includes information analyzing the effect of deleting or mutating accessory genes in the context of viral infection, which requires the engineering of CoV genomes using reverse genetics systems. However, a considerable number of publications analyze gene function by overexpressing the protein in the absence of other viral proteins. This ectopic expression provides relevant information, although does not acknowledge the complex interplay of proteins during virus infection. A critical review of the literature may be helpful to interpret apparent discrepancies in the conclusions obtained by different experimental approaches. This review summarizes the current knowledge on human CoV accessory proteins, with an emphasis on their contribution to virus-host interactions and pathogenesis. This knowledge may help the search for antiviral drugs and vaccine development, still needed for some highly pathogenic human CoVs.

Viricidal Activity of Thermoplastic Polyurethane Materials with Silver Nanoparticles.

The use of diverse Ag-based nanoparticulated forms has shown promising results in controlling viral propagation. In this study, a commercial nanomaterial consisting of ceramic-coated silver nanoparticles (AgNPs) was incorporated into thermoplastic polyurethane (TPU) plates using an industrial protocol, and the surface composition, ion-release dynamics and viricidal properties were studied. The surface characterization by FESEM-EDX revealed that the molar composition of the ceramic material was 5.5 P:3.3 Mg:Al and facilitated the identification of the embedded AgNPs (54.4 ± 24.9 nm). As determined by ICPMS, the release rates from the AgNP-TPU into aqueous solvents were 4 ppm/h for Ag and Al, and 28.4 ppm/h for Mg ions. Regarding the biological assays, the AgNP-TPU material did not induce significant cytotoxicity in the cell lines employed. Its viricidal activity was characterized, based on ISO 21702:2019, using the Spring viraemia of carp virus (SVCV), and then tested against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The results demonstrated that AgNP-TPU materials exhibited significant (75%) and direct antiviral activity against SVCV virions in a time- and temperature-dependent manner. Similar inhibition levels were found against SARS-CoV-2. These findings show the potential of AgNP-TPU-based materials as a supporting strategy to control viral spread.

DendroMap: Visual Exploration of Large-Scale Image Datasets for Machine Learning with Treemaps.

In this paper, we present DendroMap, a novel approach to interactively exploring large-scale image datasets for machine learning (ML). ML practitioners often explore image datasets by generating a grid of images or projecting high-dimensional representations of images into 2-D using dimensionality reduction techniques (e.g., t-SNE). However, neither approach effectively scales to large datasets because images are ineffectively organized and interactions are insufficiently supported. To address these challenges, we develop DendroMap by adapting Treemaps, a well-known visualization technique. DendroMap effectively organizes images by extracting hierarchical cluster structures from high-dimensional representations of images. It enables users to make sense of the overall distributions of datasets and interactively zoom into specific areas of interests at multiple levels of abstraction. Our case studies with widely-used image datasets for deep learning demonstrate that users can discover insights about datasets and trained models by examining the diversity of images, identifying underperforming subgroups, and analyzing classification errors. We conducted a user study that evaluates the effectiveness of DendroMap in grouping and searching tasks by comparing it with a gridified version of t-SNE and found that participants preferred DendroMap. DendroMap is available at https://div-lab.github.io/dendromap/.

Pulsed-Xenon Ultraviolet Light Highly Inactivates Human Coronaviruses on Solid Surfaces, Particularly SARS-CoV-2.

In the context of ongoing and future pandemics, non-pharmaceutical interventions are critical in reducing viral infections and the emergence of new antigenic variants while the population reaches immunity to limit viral transmission. This study provides information on efficient and fast methods of disinfecting surfaces contaminated with different human coronaviruses (CoVs) in healthcare settings. The ability to disinfect three different human coronaviruses (HCoV-229E, MERS-CoV, and SARS-CoV-2) on dried surfaces with light was determined for a fully characterized pulsed-xenon ultraviolet (PX-UV) source. Thereafter, the effectiveness of this treatment to inactivate SARS-CoV-2 was compared to that of conventional low-pressure mercury UVC lamps by using equivalent irradiances of UVC wavelengths. Under the experimental conditions of this research, PX-UV light completely inactivated the CoVs tested on solid surfaces since the infectivity of the three CoVs was reduced up to 4 orders of magnitude by PX-UV irradiation, with a cumulated dose of as much as 21.162 mJ/cm2 when considering all UV wavelengths (5.402 mJ/cm2 of just UVC light). Furthermore, continuous irradiation with UVC light was less efficient in inactivating SARS-CoV-2 than treatment with PX-UV light. Therefore, PX-UV light postulates as a promising decontamination measure to tackle the propagation of future outbreaks of CoVs.

MERS-CoV ORF4b is a virulence factor involved in the inflammatory pathology induced in the lungs of mice.

No vaccines or specific antiviral drugs are authorized against Middle East respiratory syndrome coronavirus (MERS-CoV) despite its high mortality rate and prevalence in dromedary camels. Since 2012, MERS-CoV has been causing sporadic zoonotic infections in humans, which poses a risk of genetic evolution to become a pandemic virus. MERS-CoV genome encodes five accessory proteins, 3, 4a, 4b, 5 and 8b for which limited information is available in the context of infection. This work describes 4b as a virulence factor in vivo, since the deletion mutant of a mouse-adapted MERS-CoV-Δ4b (MERS-CoV-MA-Δ4b) was completely attenuated in a humanized DPP4 knock-in mouse model, resulting in no mortality. Attenuation in the absence of 4b was associated with a significant reduction in lung pathology and chemokine expression levels at 4 and 6 days post-infection, suggesting that 4b contributed to the induction of lung inflammatory pathology. The accumulation of 4b in the nucleus in vivo was not relevant to virulence, since deletion of its nuclear localization signal led to 100% mortality. Interestingly, the presence of 4b protein was found to regulate autophagy in the lungs of mice, leading to upregulation of BECN1, ATG3 and LC3A mRNA. Further analysis in MRC-5 cell line showed that, in the context of infection, MERS-CoV-MA 4b inhibited autophagy, as confirmed by the increase of p62 and the decrease of ULK1 protein levels, either by direct or indirect mechanisms. Together, these results correlated autophagy activation in the absence of 4b with downregulation of a pathogenic inflammatory response, thus contributing to attenuation of MERS-CoV-MA-Δ4b.

Nature of viruses and pandemics: Coronaviruses.

Coronaviruses (CoVs) have the largest genome among RNA viruses and store large amounts of information without genome integration as they replicate in the cell cytoplasm. The replication of the virus is a continuous process, whereas the transcription of the subgenomic mRNAs is a discontinuous one, involving a template switch, which resembles a high frequency recombination mechanism that may favor virus genome variability. The origin of the three deadly human CoVs SARS-CoV, MERS-CoV and SARS-CoV-2 are zoonotic events. SARS-CoV-2 has incorporated in its spike protein a furine proteolytic site that facilitates the activation of the virus in any tissue, making this CoV strain highly polytropic and pathogenic. Using MERS-CoV as a model, a propagation-deficient RNA replicon was generated by removing E protein gene (essential for viral morphogenesis and involved in virulence), and accessory genes 3, 4a, 4b and 5 (responsible for antagonism of the innate immune response) to attenuate the virus: MERS-CoV-Δ[3,4a,4b,5,E]. This RNA replicon is strongly attenuated and elicits sterilizing protection after a single immunization in transgenic mice with the receptor for MERS-CoV, making it a promising vaccine candidate for this virus and an interesting platform for vector-based vaccine development. A strategy could be developed for the design of RNA replicon vaccines for other human pathogenic coronaviruses.

Exploring pain experience and anxiety sensitivity among Latinx adults in a federally qualified health center.

The Latinx population is the largest minority group in the United States (U.S.) and is expected to continue to grow through at least 2050. Although there is growing recognition of the importance of pain among Latinx individuals, few studies have examined individualized psychological processes governing pain severity and disability in Latinx populations. One psychological factor that has shown promise in relation to pain experience specifically and clinical conditions more generally is anxiety sensitivity. The present investigation sought to (1) characterize the severity of pain among an unselected sample of adult Latinx individuals attending a Federally Qualified Health Center (FQHC); (2) evaluate the severity of anxiety sensitivity as a function of pain severity; and (3) test the potential explanatory relevance of anxiety sensitivity as an individual difference factor for pain intensity, pain disability, psychological inflexibility for emotional distress, and global life impairment. Participants included 406 adult Spanish-speaking Latinx persons (87.2% female; Mage = 40.26 years, SD = 11.20, and 98.3% used Spanish as their first language) who attended an FQHC in Houston, Texas. Analyses revealed that 62.6% of the sample had at least some pain, and 21.9% of the same had high intensity, moderate interference, or severe interference chronic pain. Further, results provided evidence for anxiety sensitivity as a function of pain grade, such that individuals with grade 2 (high-intensity pain), grade 3 (moderate pain interference), and grade 4 (severe pain interference) chronic pain reported significantly higher levels of anxiety sensitivity than those with grade 0 pain (no chronic pain). Additionally, after controlling for age, gender, marital status, years of education, years living in the U.S., and generalized anxiety, anxiety sensitivity significantly accounted for significant variance in pain intensity, inflexibility in relation to emotional distress, and life impairment. Overall, the current study builds upon what is currently understood about anxiety sensitivity among the Latinx population and uniquely extends past work by linking individual differences in this construct to clinically relevant aspects of pain experience and life impairment among adults attending FQHC's. Additional clinical attention should be focused on anxiety sensitivity to offset pain disparities among this established health disparities group.

Perceived Discrimination, Experiential Avoidance, and Mental Health among Hispanic Adults in Primary Care.

The Hispanic population is the largest minority group in the United States and frequently experiences racial discrimination and mental health difficulties. Prior work suggests that perceived racial discrimination is a significant risk factor for poorer mental health among Hispanic in the United States. However, little work has investigated how perceived racial discrimination relates to anxiety and depression among Hispanic adults. Thus, the current study evaluated the explanatory role of experiential avoidance in the relation between perceived racial discrimination and anxiety/depressive symptoms and disorders among Hispanic adults in primary care. Participants included 202 Spanish-speaking adults (Mage = 38.99, SD = 12.43, 86.1% female) attending a community-based Federally Qualified Health Center. Results were consistent with the hypothesis that perceived racial discrimination had a significant indirect effect on depression, social anxiety, and anxious arousal symptoms as well as the number of mood and anxiety disorders through experiential avoidance. These findings suggest future work should continue to explore experiential avoidance in the association between perceived racial discrimination and other psychiatric and medical problems among the Hispanic population.

Degree of conversion of resin-cements (light-cured/dual-cured) under different thicknesses of vitreous ceramics: systematic review.

PURPOSE: This systematic review synthesized and analyzed the scientific evidence on the degree of conversion (DC) obtained by Fourier-transform infrared spectroscopy (FTIR) of light-cured and dual-cured resinous cements, photopolymerized under different thicknesses of vitreous ceramics. STUDY SELECTION: The study protocol of this systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42017069319). A comprehensive search (PubMed/MEDLINE, Scopus, EMBASE, and LILACS) was performed for papers including an in vitro design and indexed from January 2007 to December 2020 according to the study purposes. A quality appraisal (specific instrument) and descriptive analysis of the articles that met the inclusion criteria were conducted. RESULTS: Nine included studies were analyzed. Two of them used feldspathic ceramics, six used lithium disilicate, and one used both (comparing different types and opacities of ceramics). Three studies found a higher DC in dual cements, while one did not find any significant differences, and five studies found a higher DC in light-cured resin cements. Light-cured cements showed a better DC in relation to dual-cured cements in vitreous ceramic restorations with thicknesses up to 2 mm. CONCLUSION: According to the findings, the use of good photoactivation is the most relevant variable to achieve an adequate DC in light-cured and dual-cured resin cements. The use of vitreous ceramic restorations with a thickness of less than 2 mm (light-curing cements) shows a better DC. Standardized in vitro studies are required to generate accurate scientific evidence.

Evaluating the Role of Anxiety Sensitivity on Behavioral Health Outcomes among Latinx Persons.

Background: Mexican Americans represent the largest subpopulation among Latinx persons and experience numerous health inequalities for psychological symptoms and behavioral health problems. First generation Mexican Americans are particularly vulnerable to such disparities and past work suggests that the experience of acculturative stress may play a vital role in terms of mental and physical health problems among this population. The current study sought to bridge past work on acculturative stress among first-generation Mexican Americans by exploring the role of anxiety sensitivity (AS; fear of the negative consequences of internal sensations) as a potential mediational factor in terms of psychological and behavioral health problems among this group. Methods: The current study consisted of 369 first generation Mexican American persons (86.2% female, 40.1 years of age (SD = 11.1) years in the U.S. attending a Federally Qualified Healthcare Center located in an urban southwestern community. We explored whether AS served as a mediator between acculturative stress and some of the most common and disabling clinical problems among this group, including social anxiety, anxious arousal, general depression, insomnia and pain intensity and disability. Result: Consistent with prediction, there was a statistically significant indirect effect of acculturative stress via AS across all criterion variables apart from pain intensity (depression [ab = - 0.17, SE = 0.05, 95% CI [0.08, 0.26]], insomnia [ab = 0.07, SE = 0.02, 95% CI [0.03, 0.10]], social anxiety [ab 0.05, SE = 0.02, 95% CI [0.02, 0.08]], anxious arousal [ab = 0.08, SE = 0.03, 95% CI [0.03, 0.12]], pain disability [ab = 0.05, SE = 0.02, 95% CI [0.02, 0.09]]). Comparative models were run to evaluate the specificity of hypothesized statistically significant models. For all models except anxious arousal and general depression, the alternative model was rejected, adding support to the hypothesized pathway. Conclusion: Overall, this work provides initial support for the role of AS in terms of the relation between acculturative stress and numerous psychological and behavioral health problems among Mexican American adults in a clinical setting.

Update on the Inactivation Procedures for the Vaccine Development Prospects of a New Highly Virulent RGNNV Isolate.

Viral nervous necrosis (VNN) caused by the nervous necrosis virus (NNV) affects a broad range of primarily marine fish species, with mass mortality rates often seen among larvae and juveniles. Its genetic diversification may hinder the effective implementation of preventive measures such as vaccines. The present study describes different inactivation procedures for developing an inactivated vaccine against a new NNV isolate confirmed to possess deadly effects upon the European seabass (Dicentrarchus labrax), an important Mediterranean farmed fish species that is highly susceptible to this disease. First, an NNV isolate from seabass adults diagnosed with VNN was rescued and the sequences of its two genome segments (RNA1 and RNA2) were classified into the red-spotted grouper NNV (RGNNV) genotype, closely clustering to the highly pathogenic 283.2009 isolate. The testing of different inactivation procedures revealed that the virus particles of this isolate showed a marked resistance to heat (for at least 60 °C for 120 min with and without 1% BSA) but that they were fully inactivated by 3 mJ/cm2 UV-C irradiation and 24 h 0.2% formalin treatment, which stood out as promising NNV-inactivation procedures for potential vaccine candidates. Therefore, these procedures are feasible, effective, and rapid response strategies for VNN control in aquaculture.

Obturator Nerve Blockade vs. Neuromuscular Blockade for the Prevention of Adductor Spasm in Patients Undergoing Transurethral Resection of Bladder Tumors: A Randomized Controlled Trial.

BACKGROUND: The obturator nerve runs along the posterolateral walls of the bladder and electrosurgical stimulation in this region can result in adductor spasm which can occur suddenly and unexpectedly with potentially catastrophic results. METHODS: Sixty patients were prospectively randomized to receive either a single-injection ultrasound-guided obturator nerve block (ONB) or intravenous rocuronium after induction of general anesthesia (i.e., neuromuscular block [NMB]). The primary objective was to compare the incidence of adductor spasm during posterolateral bladder tumor resection when ONB or NMB was used. Secondary objectives included assessment of fall risk and incidence of adverse events. RESULTS: Five patients in the ONB group and six in the NMB group had nonlateral wall lesions. One patient in the ONB group suffered a cardiac arrest after induction of general anesthesia. Of the remaining 48 patients, six (10.2%) experienced adductor spasm. Most of these patients were in the NMB group (5/24, 20.8%), with only one patient (1/24, 4.2%) experiencing obturator reflex in the ONB group; this difference was not statistically significant (P=0.19). Patients in the ONB group had a greater decrease in mean hip adductor strength. Our study population was found to be at high risk of falls before surgery. There were no statistically significant group differences in the Timed Up and Go test, with time to perform the test increasing in both groups. CONCLUSIONS: Both techniques are safe and efficacious for preventing adductor spasm. Our data and experience suggest that the ONB is relatively easy to perform and should be considered in patients with posterolateral bladder tumors.

Modulation of the Tissue Expression Pattern of Zebrafish CRP-Like Molecules Suggests a Relevant Antiviral Role in Fish Skin.

Recent studies suggest that short pentraxins in fish might serve as biomarkers for not only bacterial infections, as in higher vertebrates including humans, but also for viral ones. These fish orthologs of mammalian short pentraxins are currently attracting interest because of their newly discovered antiviral activity. In the present work, the modulation of the gene expression of all zebrafish short pentraxins (CRP-like proteins, CRP1-7) was extensively analyzed by quantitative polymerase chain reaction. Initially, the tissue distribution of crp1-7 transcripts and how the transcripts varied in response to a bath infection with the spring viremia of carp virus, were determined. The expression of crp1-7 was widely distributed and generally increased after infection (mostly at 5 days post infection), except for crp1 (downregulated). Interestingly, several crp transcription levels significantly increased in skin. Further assays in mutant zebrafish of recombinant activation gene 1 (rag1) showed that all crps (except for crp2, downregulated) were already constitutively highly expressed in skin from rag1 knockouts and only increased moderately after viral infection. Similar results were obtained for most mx isoforms (a reporter gene of the interferon response), suggesting a general overcompensation of the innate immunity in the absence of the adaptive one.

Anxiety sensitivity and acculturative stress: Concurrent relations to mental health among Spanish-speaking Latinx in primary care.

The Latinx population suffers from mental health inequalities. Although past work has implicated acculturative stress and anxiety sensitivity as important individual difference factors for anxiety and depression in this group, it is presently unclear how they work together to influence more severe anxiety and depressive symptom expression among Latinx. To help address this gap in the existing literature, the current study evaluated the role of concurrent anxiety sensitivity and acculturative stress, in terms of anxiety and depressive symptoms and disorders, in a Latinx population in a primary care setting. Participants included 142 Latinx individuals (86.7% female; Mage = 39.66, SD = 11.34). After accounting for shared variance, the results indicated that both anxiety sensitivity and acculturative stress were significantly associated with anxious arousal symptoms, social anxiety, and depressive symptoms. However, anxiety sensitivity, but not acculturative stress, was significantly related to a number of mood and anxiety disorders. These findings suggest the importance of assessing both anxiety sensitivity and acculturative stress in routine mental health screening, as both factors may be related to poorer psychological health among this group.

Simultaneous Ca2+ Imaging and Optogenetic Stimulation of Cortical Astrocytes in Adult Murine Brain Slices.

Astrocytes are actively involved in a neuroprotective role in the brain, which includes scavenging reactive oxygen species to minimize tissue damage. They also modulate neuroinflammation and reactive gliosis prevalent in several brain disorders like epilepsy, Alzheimer's, and Parkinson's disease. In animal models, targeted manipulation of astrocytic function via modulation of their calcium (Ca2+ ) oscillations by incorporating light-sensitive cation channels like Channelrhodopsin-2 (ChR2) offers a promising avenue in influencing the long-term progression of these disorders. However, using adult animals for Ca2+ imaging poses major challenges, including accelerated deterioration of in situ slice health and age- related changes. Additionally, optogenetic preparations necessitate usage of a red-shifted Ca2+ indicator like Rhod-2 AM to avoid overlapping light issues between ChR2 and the Ca2+ indicator during simultaneous optogenetic stimulation and imaging. In this article, we provide an experimental setting that uses live adult murine brain slices (2-5 months) from a knock-in model expressing Channelrhodopsin-2 (ChR2(C128S)) in cortical astrocytes, loaded with Rhod-2 AM to elicit robust Ca2+ response to light stimulation. We have developed and standardized a protocol for brain extraction, sectioning, Rhod-2 AM loading, maintenance of slice health, and Ca2+ imaging during light stimulation. This has been successfully applied to optogenetically control adult cortical astrocytes, which exhibit synchronous patterns of Ca2+ activity upon light stimulation, drastically different from resting spontaneous activity. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Experimental preparation, setup, slice preparation and Rhod-2 AM staining Basic Protocol 2: Image acquisition and analysis.

Vaginal metastasis of gestational trophoblastic neoplasia resulting in hemorrhage: A case report.

Complete molar pregnancies complicate approximately 1 in 1500 pregnancies in the United States and result in gestational trophoblastic neoplasia in about 15-20% of these cases. Vaginal metastasis is the second most common site of metastasis and may present with vaginal bleeding and hemorrhage. This report describes a case of a 19-year-old Hispanic primigravida who presented with hemorrhage from an anterior vaginal wall metastasis two weeks after dilation and curettage for complete molar pregnancy. Hemorrhage resolved after extrusion of the lesion from the anterior vaginal wall. Pathology showed markedly atypical trophoblastic tissue from the lesion. Vaginal involvement of gestational trophoblastic neoplasia can present with life-threatening hemorrhage.

Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins.

Background: Cross-reactivity against human coronaviruses with Flebogamma® DIF and Gamunex®-C, two available intravenous immunoglobulins (IVIG), has been reported. In this study, these IVIG were tested for neutralization activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). Materials & methods: Neutralization capacity of lots of IVIG manufactured prior to COVID-19 pandemic was assessed against these viruses in cell culture. Infectivity neutralization was quantified by percent reduction in plaque-forming units and/or cytopathic/cytotoxic methods. Results: All IVIG preparations showed neutralization of SARS-CoV-2 isolates. All IVIG lots produced neutralization of SARS-CoV. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: The tested IVIG contain antibodies with significant in vitro cross-neutralization capacity against SARS-CoV-2 and SARS-CoV, but not MERS-CoV. These preparations are currently under evaluation as potential therapies for COVID-19.

Canonical and Noncanonical Autophagy as Potential Targets for COVID-19.

The SARS-CoV-2 pandemic necessitates a review of the molecular mechanisms underlying cellular infection by coronaviruses, in order to identify potential therapeutic targets against the associated new disease (COVID-19). Previous studies on its counterparts prove a complex and concomitant interaction between coronaviruses and autophagy. The precise manipulation of this pathway allows these viruses to exploit the autophagy molecular machinery while avoiding its protective apoptotic drift and cellular innate immune responses. In turn, the maneuverability margins of such hijacking appear to be so narrow that the modulation of the autophagy, regardless of whether using inducers or inhibitors (many of which are FDA-approved for the treatment of other diseases), is usually detrimental to viral replication, including SARS-CoV-2. Recent discoveries indicate that these interactions stretch into the still poorly explored noncanonical autophagy pathway, which might play a substantial role in coronavirus replication. Still, some potential therapeutic targets within this pathway, such as RAB9 and its interacting proteins, look promising considering current knowledge. Thus, the combinatory treatment of COVID-19 with drugs affecting both canonical and noncanonical autophagy pathways may be a turning point in the fight against this and other viral infections, which may also imply beneficial prospects of long-term protection.