COVID-19 pandemic, an unprecedented devastation, humanity needs an urgent cure to save the mankind from this deadly disease. Over six million people have been infected worldwide, with 6.3% reported deaths till date. SARS-CoV-2 virus, responsible for Novel Coronavirus (COVID-19) disease has been isolated recently and the vaccine's development is at nascent stage. At present, there are a few anecdotal evidences that anti-viral/anti-in ammatory/anti-malarial drugs can mitigate the disease. In the present study, we envision the potency of traditional Indian medicinal compounds that can be used as an effective drug. The viral SARS Coronavirus E protein plays a key role in virus life cycle and can be a potential drug target for the development of anti-SARS-CoV-2 drugs. Using the crystal structure of the CoVE protein, we performed virtual PyRX screening of Indian medicinal compounds which are reported to have e cacy in the treatment of some viral infections. Molecular docking studies were evaluated based on scores analysed by CavityPlus. The herbal compounds used were found to be more e cient in inhibiting the virus as compared to commercially available drugs. The results showed that β-boswellic acid and Glycyrrhizic acid possessed the best binding as a ligand with target molecule having binding a nity of-9.1 kcal/mol amongst eleven compounds screened. The study demonstrated that these are found to be strong SARS-CoV-2E protein inhibitors as they revealed compatible, near perfect dock in the overlapping region of functional viral protein pockets. These potential hit compounds can pave a way for designing of anti-viral therapeutics.

Material Supplementary 4.DC1http://www.jimmunol.org/content/suppl/2010/06/16/jimmunol.090387

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Stringent control of inflammasome signaling pathway is important for maintaining immunological balance, yet the molecular mechanisms responsible for its tight regulation are still poorly understood. In this study, we found that the signaling pathway dependent on mitochondrial antiviral signaling protein (MAVS) was required for the optimal activation of apoptosis-associated specklike protein (ASC)–dependent inflammasome. In particular, TNFR-associated factor 3 was found to be a direct E3 ligase for ASC. Ubiquitination of ASC at Lys174 was critical for speck formation and inflammasome activation. Deficiency in MAVS or TNFR-associated factor 3 impaired ASC ubiquitination and cytosolic aggregates formation, resulting in reduced inflammasome response upon RNA virus infection. This study has identified a previously unrecognized role of MAVS in the regulation of inflammasome signaling and provided molecular insight into the mechanisms by which ubiquitination of ASC controls inflammasome activity through the formation of ASC specks.

This study shows the effective results of nHAC/PLA in rabbit posterolateral spinal fusion combined with rhBMP-2. It is an alternative method to autograft by compounding this osteoconductive matrix with growth factors.

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BackgroundThere have been few studies comparing the clinical and radiographic outcomes between the Dynesys dynamic stabilization system and posterior lumbar interbody fusion (PLIF). The objective of this study is to compare the clinical and radiographic outcomes of Dynesys and PLIF for lumbar degenerative disease.MethodsOf 96 patients with lumbar degenerative disease included in this retrospectively analysis, 46 were treated with the Dynesys system and 50 underwent PLIF from July 2008 to March 2011. Clinical and radiographic outcomes were evaluated. We also evaluated the occurrence of radiographic and symptomatic adjacent segment degeneration (ASD).ResultsThe mean follow-up time in the Dynesys group was 53.6 ± 5.3 months, while that in the PLIF group was 55.2 ± 6.8 months. At the final follow-up, the Oswestry disability index and visual analogue scale score were significantly improved in both groups. The range of motion (ROM) of stabilized segments in Dynesys group decreased from 7.1 ± 2.2° to 4.9 ± 2.2° (P < 0.05), while that of in PLIF group decreased from 7.3 ± 2.3° to 0° (P < 0.05). The ROM of the upper segments increased significantly in both groups at the final follow-up, the ROM was higher in the PLIF group. There were significantly more radiographic ASDs in the PLIF group than in the Dynesys group. The incidence of complications was comparable between groups.ConclusionsBoth Dynesys and PLIF can improve the clinical outcomes for lumbar degenerative disease. Compared to PLIF, Dynesys stabilization partially preserves the ROM of the stabilized segments, limits hypermobility in the upper adjacent segment, and may prevent the occurrence of ASD.

Retinoic acid-inducible gene I (RIG-I) is an intracellular RNA virus sensor that induces type I interferon-mediated host-protective innate immunity against viral infection. Although cylindromatosis (CYLD) has been shown to negatively regulate innate antiviral response by removing K-63-linked polyubiquitin from RIG-I, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. Here we show that RIG-I activity is regulated by inhibition of CYLD expression mediated by the microRNA miR-526a. We found that viral infection specifically upregulates miR-526a expression in macrophages via interferon regulatory factor (IRF)-dependent mechanisms. In turn, miR-526a positively regulates virus-triggered type I interferon (IFN-I) production, thus suppressing viral replication, the underlying mechanism of which is the enhancement of RIG-I K63-linked ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virusinduced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein, while ectopic miR526a expression inhibits the replication of EV71 virus. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and suggest a novel mechanism for the evasion of the innate immune response controlled by EV71. IMPORTANCERNA virus infection upregulates the expression of miR-526a in macrophages through IRF-dependent pathways. In turn, miR526a positively regulates virus-triggered type I IFN production and inhibits viral replication, the underlying mechanism of which is the enhancement of RIG-I K-63 ubiquitination by miR-526a via suppression of the expression of CYLD. Remarkably, virus-induced miR-526a upregulation and CYLD downregulation are blocked by enterovirus 71 (EV71) 3C protein; cells with overexpressed miR-526a were highly resistant to EV71 infection. The collective results of this study suggest a novel mechanism of the regulation of RIG-I activity during RNA virus infection by miR-526a and propose a novel mechanism for the evasion of the innate immune response controlled by EV71.