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Evasion and antagonism of host cellular immunity upon SARS-CoV-2 infection provide replication advantage to the virus and contribute to COVID-19 pathogenesis. We explored the ability of different SARS-CoV-2 proteins to antagonize the host's innate immune system and found that the ORF6 protein mitigated type-I Interferon (IFN) induction and downstream IFN signaling. Our findings also corroborated previous reports that ORF6 blocks the nuclear import of IRF3 and STAT1 to inhibit IFN induction and signaling. Here we show that ORF6 directly interacts with RIG-I and blocks downstream type-I IFN induction and signaling by reducing the levels of K63-linked ubiquitinated RIG-I. This involves ORF6-mediated targeting of E3 ligase TRIM25 for proteasomal degradation, which was also observed during SARS-CoV-2 infection. The type-I IFN antagonistic activity of ORF6 was mapped to its C-terminal cytoplasmic tail, specifically to amino acid residues 52-61. Overall, we provide new insights into how SARS-CoV-2 inhibits type-I IFN induction and signaling through distinct actions of the viral ORF6 protein., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The detection of leucine-rich repeat containing 15 (LRRC15) as a connecting link with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the possibility of its involvement in differential restriction activity of SARS-CoV-2 pathways. However, the structure-function mechanism of LRRC15 involving the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and their mode of interaction is largely unknown. Using state-of-the-art AlphaFold2 and all-atom molecular dynamics simulations, our findings provide evidences of alternative binding modes of RBD with LRR units of LRRC15 having varied affinities. Contribution of both the receptor binding regions in RBD, including receptor binding motif in accommodating the LRR domain, towards the C-terminal region, emphasizes its differential role in modulating host cell receptiveness for SARS-CoV-2, the innate immune system, as well as antiviral tone. However, further experimental validations are necessary for unravelling the unknown mechanism and distinctive features of this host receptor in the COVID-19 pandemic, involving both the transmembrane as well as cytoplasmic domain.

The COVID-19 pandemic highlights an urgent need for effective antivirals. Targeting host processes co-opted by viruses is an attractive antiviral strategy with a high resistance barrier. Picolinic acid (PA) is a tryptophan metabolite endogenously produced in mammals. Here, we report the broad-spectrum antiviral activity of PA against enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), flaviviruses, herpes simplex virus, and parainfluenza virus. Mechanistic studies reveal that PA inhibits enveloped virus entry by compromising viral membrane integrity, inhibiting virus-cellular membrane fusion, and interfering with cellular endocytosis. More importantly, in pre-clinical animal models, PA exhibits promising antiviral efficacy against SARS-CoV-2 and IAV. Overall, our data establish PA as a broad-spectrum antiviral with promising pre-clinical efficacy against pandemic viruses SARS-CoV-2 and IAV., Competing Interests: Declaration of interests The Indian Institute of Science has filed patents for the use of PA and its derivatives as broad-spectrum antiviral and listed S.T., R.N., A.B., and R.R. as inventors., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

As universities shifted to online education with the onset of the Coronavirus Disease 2019 (COVID-19) pandemic, both pedagogy and assessment patterns across disciplines underwent a change, with a shift towards collaborative digital assessments. In this context, using qualitative and quantitative methods for data collection from an assessment conducted for 55 students who worked in groups to create YouTube videos on pre-selected modules, our analysis reveals that this assessment tool had a significant impact on peer learning, motivation and group dynamics. Students were more motivated to learn and share their learning, and they could also successfully engage in recognising and addressing group dynamics, thereby cultivating more than just subject knowledge. This finding aligns with existing scholarship and the paper adds to research about pedagogy and assessment via digital education in the Indian context, which is still upcoming. [ABSTRACT FROM AUTHOR]

An effective and rapid diagnosis has great importance in tackling the ongoing COVID-19 pandemic through isolation of the infected individuals to curb the transmission and initiation of specialized treatment for the disease. It has been proven that enhanced testing capacities contribute to efficiently curbing SARS-CoV-2 transmission during the initial phases of the outbreaks. RT-qPCR is considered a gold standard for the diagnosis of COVID-19. However, in resource-limited countries expenses for molecular diagnosis limits the diagnostic capacities. Here, we present interventions of two pooling strategies as 5 sample pooling (P-5) and 10 sample pooling (P-10) in a high-throughput COVID-19 diagnostic laboratory to enhance throughput and save resources and time over a period of 6 months. The diagnostic capacity was scaled-up 2.15-folds in P-5 and 1.8-fold in P-10, reagents (toward RNA extraction and RT-qPCR) were preserved at 75.24% in P-5 and 86.21% in P-10, and time saved was 6,290.93 h in P-5 and 3147.3 h in P-10. [ABSTRACT FROM AUTHOR]

PURPOSE: To study functional changes in vision and morphological changes on optical coherence tomography (OCT) scans in patients where intravitreal therapy (IVT) with injections has been delayed due to COVID-19 pandemic lockdown. METHODS: Retrospective cross-sectional study included 77 eyes with the diagnosis of exudative age-related macular degeneration (eAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), regularly receiving IVT with anti-vascular endothelial growth factor (Anti-VEGF) injections or dexamethasone implant and were not able to receive the injections as intended due to lockdown. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and qualitative morphological features on OCT were analyzed pre- and post-therapy break off. RESULTS: The mean duration of IVT break-off was 57 days. Mean BCVA logarithm of minimum angle of resolution (logMAR) worsened from 0.33 (20/42) to 0.35 (40/44) (P = 0.02) and mean CFT increased from 297.90 µm to 402.16 µm (P < 0.01), from pretherapy break-off to return visit. Worsening of the visual acuity was seen across all the three disease cohorts, significantly more in the eyes with eAMD. CONCLUSION: Marginal decline in the visual acuity and worsening of the OCT features were observed as a result of delay in the IVT injections of DME, eAMD and RVO patients. [ABSTRACT FROM AUTHOR]

Introduction: During the Corona Virus Disease (COVID-19) pandemic, Health Care Workers (HCWs) have experienced an unexpected increase in workload which leads to feelings of uncertainty, anxiety, and isolation. Furthermore, they are more vulnerable to contract the infection and transmit it to their family and colleagues. Aim: To evaluate the effect of COVID-19 pandemic on doctors life in term of personal and professional changes. Materials and Methods: The present observational, crosssectional study was conducted on doctors in various institutes of Udaipur, Rajasthan, India. The study comprised an online questionnaire survey which consisted of three parts; the first part constituted demographic data, the second one constituted questions on the personal life status and changes, and the third part constituted questions regarding the professional life and some miscellaneous questions gauging the doctor's knowledge of the current scenario. The collected data were entered in a Microsoft excel sheet, and the results were calculated. Results: Most of the participants were between 25-34 years (47.8%) and male (71%). A majority of the doctors had a family with children (44.2%) and a spouse who was a HCW too (59.8%). A majority of the practitioners worked with patients with coronavirus (52.3%) and thus felt worried about their family members (93.3%). Although most participants knew about telemedicine (89.3%), most of the practitioners did not practice it (76.8%). Conclusion: Although HCWs do not face harassment, they suffer anxiety regarding contracting COVID-19 themselves and transmitting it to their family members. [ABSTRACT FROM AUTHOR]