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Viruses cause a variety of diseases in humans and other organisms. The most important defense mechanism against viral infections is initiated when the viral genome is sensed by host proteins, and this results in interferon production and proinflammatory cytokine responses. The sensing of the viral genome or its replication intermediates within host cells is mediated by cytosolic proteins. For example, cGAS and IFI16 recognize non-self DNA, and RIG-I and MDA5 recognize non-self RNA. Once these sensors are activated, they trigger a cascade of reactions activating downstream molecules, which eventually results in the transcriptional activation of type I and III interferons, which play a critical role in suppressing viral propagation, either by directly limiting their replication or by inducing host cells to inhibit viral protein synthesis. The immune response against viruses relies solely upon sensing of viral genomes and their downstream signaling molecules. Although DNA and RNA viruses are sensed by distinct classes of receptor proteins, there is a possibility of overlap between the viral DNA and viral RNA sensing mechanisms. In this review, we focus on various host sensing molecules and discuss the associated signaling pathways that are activated in response to different viral infections. We further highlight the possibility of crosstalk between the cGAS-STING and the RIG-I-MAVS pathways to limit viral infections. This comprehensive review delineates the mechanisms by which different viruses evade host cellular responses to sustain within the host cells.

Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies.

Bacterial resistance towards the use of synthetic drugs has created a havoc in the modern era of health sciences. Medicinal plants may pave the way for alternative source of medicines that can overcome bacterial resistance. In this regard, employing three different extraction procedure (Maceration, Decoction and Soxhlet) aqueous extract of Moringa oleifera and Azadirachta indica were prepared and observed for bacterial inhibition and antioxidant properties. Phytochemical screening results revealed the presence of phenols, flavonoids, reducing sugars and saponins. Percentage scavenging activity primarily DPPH assay shows Moringa oleifera Soxhlet 6th (MOS 6th) with the highest percentage scavenging activity. Similarly, total flavonoid content estimation results rendered Moringa oleifera Decoction (MOD) as the highest flavonoid containing sample (68.97 ± 0.9) mg RUE/ml. Antibacterial efficiency of the extracts was monitored against Streptococcus mutans (gram-positive) and Escherichia coli (E. Coli) DH5 (gram-negative) bacteria, 96-well microtiter two-fold dilution reveals lowest MIC of 625 μg ml–1 for Neem soxhlet 6th cycle (NS 6th) against Streptococcus mutans while Moringa oliefera soxhelt 2nd cycle shows a low toxicity pattern (MIC 5000 μg ml–1). However, only three extract (Neem Soxhlet 2nd cycle, Moringa oleifera Soxhlet 2nd cycle and Neem Soxhlet 6th cycle) shows inhibitory potential against E. coli. Furthermore, zone of inhibition acquired via agar-well diffusion assay well corroborates with the results of 96-well pate. Based on extraction procedure, Soxhlet method establishes a good toxicity profile against the studied organism.

Coronavirus disease 2019 (COVID-19) has overwhelmed the healthcare and economy of the world, with emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posing an everlasting threat to humanity. While most COVID-19 vaccines provide adequate protective immunological response against the original SARS-CoV-2 variant, there is a pressing need to understand their biological and clinical responses. Recent evidence suggests that some of the new variants of SARS-CoV-2 evade the protection conferred by the existing vaccines, which may impede the ongoing efforts to expedite the vaccination programs worldwide. These concerns have also highlighted the importance of a pan-COVID-19 vaccine, which is currently in the making. Thus, it is imperative to have a better molecular and clinical understanding of the various COVID-19 vaccines and their immunological trajectory against any emerging variant of concerns (VOCs) in particular to break this vicious cycle. Furthermore, other treatment regimens based on cellular therapies and monoclonal antibodies should be explored systematically as an alternative and readily available option considering the possibility of the emergence of more virulent SARS-CoV-2 mutants. In this review, we shed light on the various molecular mechanisms and clinical responses of COVID-19 vaccines. Importantly, we review the recent findings of their long-term immune protection and efficacy against emerging VOCs. Considering that other targeted and effective treatments will complement vaccine therapy, we provide a comprehensive understanding of the role of cell-based therapies, monoclonal antibodies, and immunomodulatory agents as alternative and readily available treatment modalities against any emerging SARS-CoV-2 variant.

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1,3,4-Oxadiazole-based heterocyclic analogs (3a–3m) were synthesized via cyclization of Schiff bases with substituted aldehydes in the presence of bromine and acetic acid. The structural clarification of synthesized molecules was carried out with various spectroscopic techniques such as FT-IR, 1H and 13C-NMR, UV–visible spectroscopy, mass spectrometry (LCMS). The TD-DFT studies were also confirmed the structure of drug molecules. In vitro antifungal activity was performed against C. Albicans, C. glabrata and C. tropicalis and analogs 3g, 3i, and 3m showed potent MIC at 200 µg/ml and excellent ZOI measurements of 17-21 nm. The cell viability on human hepatoma cells (Huh7) for lead molecules 3g, 3i, and 3m was found to be 99.5%, 92.3%, and 86.9% at 20 μM, 10 μM, and 20 μM respectively. The antioxidant activity of the lead molecules 3g, 3i, and 3m were estimated and exhibited great IC50 values of 0.104 ± 0.021, 0.145 ± 0.05, and 0.165 ± 0.018 μg/mL with DPPH and 0.107 ± 0.04, 0.191 ± 0.12, and 0.106 ± 0.08 with H2O2 respectively. The DNA binding interaction mode for the lead molecules was also carried out with Ct-DNA using the absorption, emission, CV, CD, and Time resolve fluorescence techniques. The results showed good binding constant (Kb) values 9.1×105, 9.94×105, and 9.32×105 M−1 for 3g, 3i, and 3m respectively. The results were further validated by In-silico molecular docking and pharmacokinetics properties of lead drug molecules were also studied with PDB ID: 1BNA and 5FSA to explore the best hits.