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The recent ongoing pandemic caused by SARS-CoV-2 continues to impose devastating impacts and is accountable for the loss of more than 250,000 human lives within a short span of four months. This urges immediate therapeutic measures to control the impact of this disease. One of the most conserved and potentially druggable sites is the Nsp16 active site that performs the 2’-O-methyltransferase activity and puts a 5’ cap on the viral RNA molecules. This allows them to mimic endogenous transcripts for the efficient translation of viral proteins and evasion of the immune response. Herein, we screened three libraries of compounds (>5500) with chemical diversity to identify hits against Nsp16 active site of SARS-CoV-2. From each library a top hit was identified, namely Velpatasvir from the FDA compounds; JFD00244 from the LOPAC library and compound 6 from the SAM based analog library. Interestingly, all three hits showed higher affinity than the positive controls. Velpatasvir is a known anti-viral drug used against Hepatitis C virus, and JFD00244 is a SIRT2 inhibitor. 100ns molecular simulation studies showed all three molecules to have stable and energetically favourable interactions with the active site of Nsp16. In summary, this investigation identified three potential drug candidates that are predicted to be potent Nsp16 inhibitors and could be pursued further in cell-based studies.

We utilized volcanic CO2 vents at Castello Aragonese off Ischia Island as a natural laboratory to investigate the effect of lowered pH/elevated CO2 on the bioactivities of extracts from fleshy brown algae Sargassum vulgare C. Agardh. We analysed the carbohydrate levels, antioxidant capacity, antibacterial, antifungal, antiprotozoal, anticancer properties and antimutagenic potential of the algae growing at the acidified site (pH similar to 6.7) and those of algae growing at the nearby control site Lacco Ameno (pH similar to 8.1). The results of the present study show that the levels of polysaccharides fucoidan and alginate were higher in the algal population at acidified site. In general, extracts for the algal population from the acidified site showed a higher antioxidant capacity, antilipidperoxidation, antibacterial, antifungal, antiprotozoal, anticancer activities and antimutagenic potential compared to the control population. The increased bioactivity in acidified population could be due to elevated levels of bioactive compounds of algae and/or associated microbial communities. In this snapshot study, we performed bioactivity assays but did not characterize the chemistry and source of presumptive bioactive compounds. Nevertheless, the observed improvement in the medicinal properties of S. vulgare in the acidified oceans provides a promising basis for future marine drug discovery. (C) 2019 Elsevier Ltd. All rights reserved.

Corrosion inhibition effect of Justicia gendarussa extract (JGPE) on mild steel in 1 M HCl medium has been investigated by weight loss and electrochemical techniques. Inhibition efficiency of 93% was achieved with 150 ppm JGPE at 25 °C. The polarization studies showed that JGPE acts as mixed-type inhibitor. The Nyquist plots showed that on increasing JGPE concentration, increases charge transfer resistance and decreases double layer capacitance. JGPE obeys the Langmuir adsorption isotherm. AFM and ESCA confirmed the adsorption of JGPE on mild steel surface. Finally, JGPE inhibition efficiency was discussed in terms of adsorption and protective film formation.

Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death. In contrast, eEF1A2 protein favors oncogenesis as shown by the fact that overexpression of eEF1A2 leads to cellular transformation and gives rise to tumors in nude mice. The eEF1A2 protein stimulates the phospholipid signaling and activates the Akt-dependent cell migration and actin remodeling that ultimately favors tumorigenesis. In contrast, inactivation of eEF1A proteins leads to immunodeficiency, neural and muscular defects, and favors apoptosis. Finally, eEF1A proteins interact with several viral proteins resulting in enhanced viral replication, decreased apoptosis, and increased cellular transformation. This review summarizes the recent findings on eEF1A proteins indicating that eEF1A proteins play a critical role in numerous human diseases through enhancement of oncogenesis, blockade of apoptosis, and increased viral pathogenesis.

Most of the studies regarding the impact of ocean acidification on macroalgae have been carried out for short-term periods, in controlled laboratory conditions, thus hampering the possibility to scale up the effects on long-term. In the present study, the volcanic CO2 vents off Ischia Island were used as a natural laboratory to investigate the metabolic response of the brown alga Sargassum vulgare to acidification at different time scales. For long-term effects, algal populations naturally growing at acidified and control sites were compared. For short-term responses, in situ reciprocal transplants from control to acidified site and vice-versa were performed. Changes in the levels of sugars, fatty acids (FAs), amino acids (AAs), antioxidants, and phenolic compounds were examined. Our main finding includes variable metabolic response of this alga at different time scales to natural acidification. The levels of sugars, FAs, and some secondary metabolites were lower in the natural population at the acidified site, whereas the majority of AAs were higher than those detected in thalli growing at control site. Moreover, in algae transplanted from control to acidified site, soluble sugars (glucose and mannose), majority of AAs, and FAs increased in comparison to control plants transplanted within the same site. The differences in the response of the macroalga suggest that the metabolic changes observed in transplants may be due to acclimation that supports algae to cope with acidification, thus leading to adaptation to lowered pH in long time scale. (c) 2018 Elsevier B.V. All rights reserved.

Research to date has suggested that both individual marine species and ecological processes are expected to exhibit diverse responses to the environmental effects of climate change. Evolutionary responses can occur on rapid (ecological) timescales, and yet studies typically do not consider the role that adaptive evolution will play in modulating biological responses to climate change. Investigations into such responses have typically been focused at particular biological levels (e.g., cellular, population, community), often lacking interactions among levels. Since all levels of biological organisation are sensitive to global climate change, there is a need to elucidate how different processes and hierarchical interactions will influence species fitness. Therefore, predicting the responses of communities and populations to global change will require multidisciplinary efforts across multiple levels of hierarchy, from the genetic and cellular to communities and ecosystems. Eventually, this may allow us to establish the role that acclimatisation and adaptation will play in determining marine community structures in future scenarios.

Ocean acidification is an emerging problem that is expected to impact ocean species to varying degrees. Currently, little is known about its effect on molecular mechanisms induced in fleshy macroalgae. To elucidate genome wide responses to acidification, a comparative transcriptome analysis was carried out between Sargassum vulgare populations growing under acidified conditions at volcanic CO2 vents and a control site. Several transcripts involved in a wide range of cellular and metabolic processes were differentially expressed. No drastic changes were observed in the carbon acquisition processes and RuBisCO level. Moreover, relatively few stress genes, including those for antioxidant enzymes and heat shock proteins, were affected. Instead, increased expression of transcripts involved in energy metabolism, photosynthetic processes, and ion homeostasis suggested that algae increased energy production to maintain ion-homeostasis and other cellular processes. Also, an increased allocation of carbon to cell wall and carbon storage was observed. A number of genes encoding proteins involved in cellular signaling, information storage and processing, and transposition were differentially expressed between the two conditions. The transcriptional changes of key enzymes were largely confirmed by enzymatic activity measurements. Altogether, the changes induced by acidification indicate an adaptation of growth and development of S. vulgare at the volcanic CO2 vents, suggesting that this fleshy alga exhibits a high plasticity to low pH and can adopt molecular strategies to grow also in future more acidified waters. This article is protected by copyright. All rights reserved.