Characterization and ecological risk assessment of microplastics accumulated in sea water, sand, sediment, shell water and selected tissues of hermit crab of Sundarban Biosphere Reserve.

Sundarban, a Ramsar site of India, has been encountering an ecological threat due to the presence of microplastic (MP) wastes generated from different anthropogenic sources. Clibanarius longitarsus, an intertidal hermit crab of Sundarban Biosphere Reserve, resides within the abandoned shell of a gastropod mollusc, Telescopium telescopium. We characterized and estimated the MP in the gills and gut of hermit crab, as well as in the water present in its occupied gastropod shell. The average microplastic abundance in sea water, sand and sediment were 0.175 ± 0.145 MP L-1, 42 ± 15.03 MP kg-1 and 67.63 ± 24.13 MP kg-1 respectively. The average microplastic load in hermit crab was 1.94 ± 0.59 MP crab-1, with 33.89 % and 66.11 % in gills and gut respectively. Gastropod shell water exhibited accumulation of 1.69 ± 1.43 MP L-1. Transparent and fibrous microplastics were documented as the dominant polymers of water, sand and sediment. Shell water exhibited the prevalence of green microplastics followed by transparent ones. Microscopic examination revealed microplastics with 100-300 µm size categories were dominant across all abiotic compartments. ATR-FTIR and Raman spectroscopy confirmed polyethylene and polypropylene as the prevalent polymers among the five identified polymers of biotic and abiotic components. The target group index indicated green and black as the preferable microplastics of crab. The ecological risk analysis indicated a considerable level of environmental pollution risk in Sundarban and its inhabiting organisms. This important information base may facilitate in developing a strategy of mitigation to limit the MP induced ecological risk at Sundarban Biosphere Reserve.

Hazards of antiviral contamination in water: Dissemination, fate, risk and their impact on fish.

Antiviral drugs are a cornerstone in the first line of antiviral therapy and their demand rises consistently with increments in viral infections and successive outbreaks. The drugs enter the waters due to improper disposal methods or via human excreta following their consumption; consequently, many of them are now classified as emerging pollutants. Hereby, we review the global dissemination of these medications throughout different water bodies and thoroughly investigate the associated risk they pose to the aquatic fauna, particularly our vertebrate relative fish, which has great economic and dietary importance and subsequently serves as a major doorway to the human exposome. Our risk assessment identifies eleven such drugs that presently pose high to moderate levels of risk to the fish. The antiviral drugs are likely to induce oxidative stress, alter the behaviour, affect different physiological processes and provoke various toxicological mechanisms. Many of the compounds exhibit elevated bioaccumulation potential, while, some have an increased tendency to leach through soil and contaminate the groundwater. Eight antiviral medications show a highly recalcitrant nature and would impact the aquatic life consistently in the long run and continue to influence the human exposome. Thereby, we call for urgent ecopharmacovigilance measures and modification of current water treatment methods.

Immunoinformatics approaches in developing a novel multi-epitope chimeric vaccine protective against Saprolegnia parasitica.

Saprolegnia parasitica is responsible for devastating infections in fish and poses a tremendous threat to the global aquaculture industry. Presently, no safe and effective control measures are available, on the contrary, use of banned toxic compounds against the pathogen is affecting humans via biomagnification routes. This pioneering study aims to design an effective multi-epitope multi-target vaccine candidate against S. parasitica by targeting key proteins involved in the infection process. The proteins were analyzed and linear B-cell epitopes, MHC class I, and class II epitopes were predicted. Subsequently, highly antigenic epitopes were selected and fused to a highly immunogenic adjuvant, 50S ribosomal protein L7/L12, to design a multi-epitope chimeric vaccine construct. The structure of the vaccine was generated and validated for its stereochemical quality, physicochemical properties, antigenicity, allergenicity, and virulence traits. Molecular docking analyses demonstrated strong binding interactions between the vaccine and piscine immune receptors (TLR5, MHC I, MHC II). Molecular dynamics simulations and binding energy calculations of the complexes, further, reflected the stability and favorable interactions of the vaccine and predicted its cytosolic stability. Immune simulations predicted robust and consistent kinetics of the immune response elicited by the vaccine. The study posits the vaccine as a promising solution to combat saprolegniasis in the aquaculture industry.

Immunoinformatics and reverse vaccinology approach in designing a novel highly immunogenic multivalent peptide-based vaccine against the human monkeypox virus.

Background: Monkeypox is a highly infectious zoonotic disease, often resulting in complications ranging from respiratory illnesses to vision loss. The escalating global incidence of its cases demands prompt attention, as the absence of a proven post-exposure treatment underscores the criticality of developing an effective vaccine. Methods: Interactions of the viral proteins with TLR2 and TLR4 were investigated to assess their immunogenic potentials. Highly immunogenic proteins were selected and subjected to epitope mapping for identifying B-cell and MHC class I and II epitopes. Epitopes with high antigenicity were chosen, considering global population coverage. A multi-target, multi-epitope vaccine peptide was designed, incorporating a beta-defensin 2 adjuvant, B-cell epitopes, and MHC class I and II epitopes. Results: The coordinate structure of the engineered vaccine was modeled and validated. In addition, its physicochemical properties, antigenicity, allergenicity, and virulence traits were evaluated. Molecular docking studies indicated strong interactions between the vaccine peptide and the TLR2 receptor. Furthermore, molecular dynamics simulations and immune simulation studies reflected its potent cytosolic stability and robust immune response dynamics induced by the vaccine. Conclusion: This study explored an innovative structure-guided approach in the use of immunoinformatics and reverse vaccinology in pursuit of a novel multi-epitope vaccine against the highly immunogenic monkeypox viral proteins. The simulation studies indicated the engineered vaccine candidate to be promising in providing prophylaxis to the monkeypox virus; nevertheless, further in vitro and in vivo investigations are required to prove its efficacy.

Structural Insights to the Pathophysiology of Effector Induced Immunostimulation in Salmonella Typhimurium: Biocomputational Methods.

INTRODUCTION: The worldwide impact of the foodborne pathogen Salmonella can never be overstated, nor can be the fatal threat of septicemia in patients infected with its Typhimurium serovar. Behind the hyperimmune response in the case of septicemia lies a critical phenomenon of the bacterial pathogenic signals being sensed by different pattern recognition receptors, such as the Typhimurium effector proteins that are detected by toll-like receptors. METHODS: To mitigate such a threat, precise structural and functional description of these effectors is necessary. The same has been addressed in this article using accelerated biocomputational techniques, beginning with the identification of the functional niche of the effectors and their influence over other proteins. RESULTS: The molecular crystal structures were retrieved, and rigorous molecular docking experiments were conducted among the TLRs and effector proteins in order to examine the interactions. The interactions were thereby evaluated and screened according to their respective strengths using parameters including binding affinity, dissociation constant, hydropathy variation, etc. SopB effectors were found to be detected by three different TLR proteins and GtgE by two other TLRs, while SifA, SrfJ, and SsaV had only a single interacting TLR partner each. Interestingly, TLR9 presented lower sensitivity towards PAMPs of this bacterium. CONCLUSION: Normal modal analyses in combination with atomistic molecular dynamics simulations that tend to imitate natural cytosolic environments reveal stable and consistent interactions and realistic conformations among the effector-bound TLR complexes. The findings open up new avenues for the development of targeted therapies against Salmonella, which could significantly reduce the global burden of this foodborne pathogen.

Designing AbhiSCoVac - A single potential vaccine for all 'corona culprits': Immunoinformatics and immune simulation approaches.

The coronaviridae family has generated highly virulent viruses, including the ones responsible for three major pandemics in last two decades with SARS in 2002, MERS outbreak in 2012 and the current nCOVID19 crisis that has turned the world breadthless. Future outbreaks are also a plausible threat to mankind. As computational biologists, we are committed to address the need for a universal vaccine that can deter all these pathogenic viruses in a single shot. Notably, the spike proteins present in all these viruses function as credible PAMPs that are majorly sensed by human TLR4 receptors. Our study aims to recognize the amino acid sequence(s) of the viral spike proteins that are precisely responsible for interaction with human TLR4 and to screen the immunogenic epitopes present in them to develop a multi-epitope multi-target chimeric vaccine against the coronaviruses. Molecular design of the constructed vaccine peptide is qualified in silico; additionally, molecular docking and molecular dynamics simulation studies collectively reveal strong and stable interactions of the vaccine construct with TLRs and MHC receptors. In silico cloning is performed for proficient expression in bacterial systems. In silico immune simulation of the vaccine indicates highly immunogenic nature of the vaccine construct without any allergic response. The present biocomputational study hereby innovates a vaccine candidate - AbhiSCoVac hypothesized as a potent remedy to combat all the virulent forms of coronaviruses.

Taming the Storm in the Heart: Exploring Different Therapeutic Choices Against Myocardial Inflammation in COVID-19.

Mechanism of cardiac injury in COVID-19 is a serious problem and plays critical role in mediating the severity of the disease. However, the mechanistic insights of the induction of the inflammatory signal leading to cardiac injury was poorly understood. However, few recent studies have indicated the involvement of Toll-Like Receptors (TLRs) as the major 'culprit' behind eliciting the initial signal of 'cytokine storm'. As a result, TLRs are now considered as the therapeutic targets to develop efficacious therapeutics. Herein, we present an overall summary on the mechanistic insight of cardiac injury in COVID-19 patients and the therapeutic promises of TLR-targeted therapies.

Chemotherapy vs. Immunotherapy in combating nCOVID19: An update.

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis.

In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by the intracellular TLRs of humans.

The coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has already resulted in a huge setback to mankind in terms of millions of deaths, while the unavailability of an appropriate therapeutic strategy has made the scenario much more severe. Toll-like receptors (TLRs) are crucial mediators and regulators of host immunity and the role of human cell surface TLRs in SARS-CoV-2 induced inflammatory pathogenesis has been demonstrated recently. However, the functional significance of the human intracellular TLRs including TLR3, 7, 8, and 9 is yet unclear. Hitherto, the involvement of these intracellular TLRs in inducing pro-inflammatory responses in COVID-19 has been reported but the identity of the interacting viral RNA molecule(s) and the corresponding TLRs have not been explored. This study hopes to rationalize the comparative binding of the major SARS-CoV-2 mRNAs to the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drives these interactions. Our in silico study on the binding of all mRNAs with the intracellular TLRs depicts that the mRNA of NSP10, S2, and E proteins of SARS-CoV-2 are possible virus-associated molecular patterns that bind to TLR3, TLR9, and TLR7, respectively, and trigger downstream cascade reactions. Intriguingly, binding of the viral mRNAs resulted in variable degrees of conformational changes in the ligand-binding domain of the TLRs ratifying the activation of the downstream inflammatory signaling cascade. Taken together, the current study is the maiden report to describe the role of TLR3, 7, and 9 in COVID-19 immunobiology and these could serve as useful targets for the conception of a therapeutic strategy against the pandemic.

In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs.

Coronavirus disease-2019 (COVID-19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS-CoV-2), its mode of interaction with the angiotensin-converting enzyme-2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, the involvement of the human Toll-like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS-CoV-2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS-CoV-2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS-CoV-2 from a bat and also revealed that TLR4 may have a crucial role in the virus-induced inflammatory consequences associated with COVID-19. Therefore, selective targeting of TLR4-spike protein interaction by designing competitive TLR4-antagonists could pave a new way to treat COVID-19. Finally, this study is expected to improve our understanding on the immunobiology of SARS-CoV-2 and could be useful in adopting spike protein, ACE2, or TLR-guided intervention strategy against COVID-19 shortly.