The evolution of the SARS‐CoV‐2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants ...interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor‐binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS‐CoV‐2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N‐E484K‐N501Y), Brazilian (K417T‐E484K‐N501Y), and hypothetical (N501Y‐E484K) variants alter the binding affinity, create new inter‐protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N‐E484K‐N501Y), Brazilian (K417T‐E484K‐N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection‐driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.
This study precisely explored the mechanism of the interaction of the spike RBD with the host ACE2 and revealed the differences in the binding of the reference and new variants. The systematic investigation revealed that the South African and Brazilian variants are more lethal than the others due to inter‐protein contacts specifically the electrostatic while the N501Y is comparable with the wild type. We hypothesized that the residue at 501Y is continuously subjected to positive selection pressure. We further demonstrated the dynamic behavior is also changed with the protein evolution. Conclusively, this study provides strong basis for structure and rationale‐based drug designing against the new variant by exploring the noticeable differences.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented setback for global economy and health. Vaccination is ...one of the most effective interventions to substantially reduce severe disease and death due to SARS‐CoV‐2 infection. Vaccination programmes are being rolled out globally, but most of these vaccines have been approved without extensive studies on their side‐effects and efficacy. Recently, new‐onset autoimmune phenomena after COVID‐19 vaccination have been reported increasingly (e.g. immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain–Barré syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus). Molecular mimicry, the production of particular autoantibodies and the role of certain vaccine adjuvants seem to be substantial contributors to autoimmune phenomena. However, whether the association between COVID‐19 vaccine and autoimmune manifestations is coincidental or causal remains to be elucidated. Here, we summarize the emerging evidence about autoimmune manifestations occurring in response to certain COVID‐19 vaccines. Although information pertaining to the risk of autoimmune disease as a consequence of vaccination is controversial, we merely propose our current understanding of autoimmune manifestations associated with COVID‐19 vaccine. In fact, we do not aim to disavow the overwhelming benefits of mass COVID‐19 vaccination in preventing COVID‐19 morbidity and mortality. These reports could help guide clinical assessment and management of autoimmune manifestations after COVID‐19 vaccination.
As vaccination programmes are being rolled out globally, new‐onset autoimmune phenomena are emerging after COVID‐19 vaccination (e.g. immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain–Barré syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak.
An online survey was run from February 19 to March 6, 2020; a ...total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2).
Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05).
During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
•We consider price and quality decisions in a dual-channel supply chain.•We show the impacts of adding a new channel on price, quality and profit.•We identify two Pareto zones of adding a new ...channel.
Since the decision of non-price feature such as product quality draws a little attention in the literature of dual-channel supply chains, this paper investigates price and quality decisions in dual-channel supply chains, in which a single product is delivered through a retail channel, a direct channel, or a dual channel with both retail and direct channels. Considering the supply chains can be centralized or decentralized, we demonstrate that quality improvement can be realized when a new channel is introduced. Moreover, we employ two themes in terms of channel-adding Pareto zone to characterize the impacts of channel structures on supply-chain performance, including the whole system's profit (for the centralized system), each player's profit (for the decentralized system), and consumer surplus. When price and quality decisions are considered, we find the supply chain performance could be improved due to a new channel augmented. Moreover, we show the effects of the quality sensitivity parameters of different channels on price and product quality, as well as profits and consumer surplus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A single‐junction polymer solar cell with an efficiency of 10.1% is demonstrated by using deterministic aperiodic nanostructures for broadband light harvesting with optimum charge extraction. The ...performance enhancement is ascribed to the self‐enhanced absorption due to collective effects, including pattern‐induced anti‐reflection and light scattering, as well as surface plasmonic resonance, together with a minimized recombination probability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In practice, manufacturers may encroach on retail markets through a variety of methods, one being through the use of an online channel direct to the consumers, called encroachment. Current research ...typically assumes that downstream retailers retain procurement from the encroaching supplier. In reality, however, retailers may have the option of switching suppliers after encroachment. By considering a supply chain consisting of one manufacturer and one retailer with outside options, this paper analyzes the effects of the option of switching suppliers on the supply chain players' strategic interactions under the threat of supplier encroachment. We consider that the manufacturer makes encroachment decision preceding the retailer's switch decision. We capture various outcomes of the encroachment and switch decisions by using a classic encroachment model with quantity decisions (Cournot model). Specifically, we identify two effects of the outside option on the strategic encroachment decision. The first, the deterrence effect, means that the manufacturer's encroachment is deterred by the threat of switching supplies altogether; while the second, the permissive effect, indicates that the retailer intends to switch to the alternative source after the encroachment. Interestingly, we show that the encroachment could improve the total profit of the incumbent manufacturer and the retailer even when the retailer's switch has occurred. In this case, however, the manufacturer profits while the retailer is hurt by the encroachment and the switch. Finally, we also investigate several extended cases to demonstrate the robustness of our findings.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Gram-negative bacteria use various secretion systems to deliver their secreted effectors. Among them, type IV secretion system exists widely in a variety of bacterial species, and secretes type IV ...secreted effectors (T4SEs), which play vital roles in host-pathogen interactions. However, experimental approaches to identify T4SEs are time- and resource-consuming. In the present study, we aim to develop an
stacked ensemble method to predict whether a protein is an effector of type IV secretion system or not based on its sequence information. The protein sequences were encoded by the feature of position specific scoring matrix (PSSM)-composition by summing rows that correspond to the same amino acid residues in PSSM profiles. Based on the PSSM-composition features, we develop a stacked ensemble model PredT4SE-Stack to predict T4SEs, which utilized an ensemble of base-classifiers implemented by various machine learning algorithms, such as support vector machine, gradient boosting machine, and extremely randomized trees, to generate outputs for the meta-classifier in the classification system. Our results demonstrated that the framework of PredT4SE-Stack was a feasible and effective way to accurately identify T4SEs based on protein sequence information. The datasets and source code of PredT4SE-Stack are freely available at http://xbioinfo.sjtu.edu.cn/PredT4SE_Stack/index.php.
The evolution of new SARS‐CoV‐2 variants around the globe has made the COVID‐19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to ...the receptor‐binding motif (RBM) of the receptor‐binding domain (RBD) spike glycoprotein, i. e. L452R‐E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R‐E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic‐stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural‐dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS‐CoV‐2 variants.
Structural and biomolecular simulation techniques were used in this study to explore the impact of specific mutations in the B.1.617 variant of SARS‐CoV‐2 on the binding of receptor‐binding domain (RBD) to the host receptor ACE2. The analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic stability, residual flexibility, and structural compactness.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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