Integration of RFID strategic value attributes mechanism decision in apparel supply chain: fuzzy AHP-TOPSIS approach

PurposeThe purpose of this paper is to identify the radio frequency identification (RFID) strategic value attributes (RFIDSVAs) mechanism selections preferences and also integration of RFID tags with technology coordination tools (IRTWTCTs) alternatives ranking performance decisions in supply chain management (SCM). RFID-enabled techno-economic feasibility decisions are enhancing the SC visibility in apparel supply chains (ASCs). The RFIDSVAs mechanism selections have performed significant agility to strategic competitive advantages, namely, inventory visibility, multi-tags ownership transfer within trusted third party, etc.Design/methodology/approachFuzzy analytical hierarchy process (FAHP) and FAHP-fuzzy Technique for Order of Preference by Similarity to Ideal Solution (FTOPSIS) approaches have been used to evaluate the quantitative assessment of RFIDSVA mechanisms selection decision based on weight priority orders and IRTWTCTs alternatives selection in ASC networks. The comparison of FAHP and FAHP-FTOPSIS approaches to evaluate the integrated framework develop in RFIDSVAs mechanisms and IRTWTCTs alternatives selection decisions in Indian multi-tier ASC networks.FindingsThe result found that the FAHP-FTOPSIS approaches have used to prioritizing the RFIDSVA mechanism selection weights and also identify the IRTWTCTs alternatives ranking preferences order in apparel SCM. The comparison between the FAHP and FAHP-FTOPSIS approach to quantitative assessments from RFIDSVA mechanisms and IRTWTCTs alternatives selection decisions, which enable them SC agility potential across multi-tier visibility in ASC networks. ASC stakeholders can be benefited by techno-economic feasibility decisions, RFID-enabled shop floor activities, multi-tags ownerships transfer in SCs and knowledge-based cryptography tags/items separation in SCs.Research limitations/implicationsThe research work has considered only five RFIDSVA mechanisms and also three integration of RFIDTWTCTs alternatives in multi-tier ASC. The strategic competitive advantages are achieved by RFID-enabled break-even tags price decisions and also techno-economic feasibility decision by contractual design multi-tier SC stakeholder's involvements.Practical implicationsThe pilot project study explores that the quantitative assessment decision has based on RFID-enable techno-economic feasibility in ASCs. Stakeholders can be benefited by inventory control of the financial losses, reducing the inventory inaccuracies and multi-tags ownership transfer within trusted third-party traceability in ASC networks.Originality/valueThis study explores the RFID-enabled apparel SC process and activities visibility (natural fibre's fibre producer, fibre dyeing producer, yarn spinning producer, knitting and finishing producer).

Economically viable flower drying techniques to sustain flower industry amid COVID-19 pandemic.

Imposing lockdown amid COVID-19 pandemic has severely affected flower cultivation and their trades. Flower plants are very sensitive to the harvesting, and any unexpected delay may cause great loss (~ 50-60%) to the farmers. In 2018-2019, the worth of total production of floriculture products was ~ Rs 571.38 crore. During lockdown, the availability of human laborers and restricted transport has disrupted the supply of flowers to the market. Hence, some alternative options are suggested here for the farmers, for example, conversion of decorative flowers (e.g., anthurium, China aster, globe amaranthus, sweet-william, anemone, sea lavender, etc.) and inflorescence (e.g., Michaelmas daisy, zinnia, statice, ferns, aspidistra, eucalyptus, magnolia, etc.) can also be into value-added products through drying and dehydration technologies. Many dehydration methods such as hot air oven, solar drying, press drying, freeze-drying, embedded drying, glycerine drying, and microwave oven drying polyester drying can be used for flower drying at room temperature (~ 25 °C). These floral and foliage dehydration techniques are quite simple, which can also be operated by unskilled persons. Moreover, it will generate self-employment for the youth and women along with increased revenue than selling fresh flowers. In this review, different techniques of flower drying have been discussed in detail along with the influencing factors, efficiency, economic feasibility, flower waste management and sustainability. Further, it has also been suggested how these techniques could be useful for farmers, researchers, and traders to create value-added products? Hence, the present paper could be very interesting for the flower growers, retailers, students, as well as floricultural scientists who are involved in flower production worldwide.

Do the macro and global economic factors drive the nonperforming loans in GCC economies?

PurposeThe current study aims to investigate the determinants of nonperforming loans (NPLs) in the GCC economies during the period spanning 2000 to 2018. It also examines whether the worldwide financial crisis of 2007–2008, which brought the issue of non–performing loans to the greater attention of academics and policymakers, had a substantial impact on NPLs in this region.Design/methodology/approachThe sample consists of 53 conventional banks from GCC countries, and the basic data for the study is obtained from various sources such as Bankscope, IMF World Economic Outlook, World Bank and Chicago Board of Options Exchange Market Volatility Index. The estimations were done by dynamic panel data regression modeling using system generalized methods of moments.FindingsThe findings reveal that both, the non-oil real GDP growth rate and inflation have favorable effects on NPLs. On the other hand, domestic credit to the private sector and the volatility index have an adverse effect on NPLs. Furthermore, the period-wise analysis shows that the relevance and significance of the determinants of NPLs vary between the precrisis and postcrisis periods. It is also reflected through the intercept dummy, which is found to be significant, indicating that the financial crisis, as a global economic factor, had a significant impact on NPLs. A number of robustness tests are applied, which indicate that the results are mostly robust and consistent in terms of the significance of the explanatory variables and the direction of their relationship with the dependent variable.Practical implicationsPolicymakers and bank authorities must strive to maintain a healthy economy and implement macroprudential policies to improve the financial stability of banks and reduce credit risk.Originality/valueTo the best of the authors' knowledge, this is likely the first study that empirically investigates the influence of the financial crisis on NPLs in the context of GCC economies. In addition, the research spans 19 years to produce more conclusive results.

Good outcomes of living donor liver transplant in primary sclerosing cholangitis: an experience from North India.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. In the absence of effective medical therapy, liver transplant is the definitive treatment for advanced stage. However, recurrence of PSC after liver transplant is of concern which can lead to graft failure and may require retransplant. There are limited data on outcomes of living donor liver transplant (LDLT) in PSC. Also, in LDLT as donors are genetically related there can be an increased risk of recurrence. We conducted this retrospective study to analyze the outcomes of LDLT in PSC at a tertiary liver transplant center in north India. METHODS: We conducted a retrospective analysis of 3213 transplant recipients who underwent LDLT from January 2006 to May 2021. Of these 26 (0.80%) patients had PSC as indication for liver transplantation (PSC = 24, PSC-AIH overlap = 2). Data analysis was done to look for baseline demographics, clinical details, transplant outcomes, PSC recurrence, and survival. RESULTS: Mean age of study group was 42 (± 13.8) years and 19 patients (73.1%) were males. All patients had decompensated cirrhosis at the time of transplant. Mean CTP score and MELD score were 9.5 (± 1.8) and 18.9 (± 7.1), respectively. Sixteen patients received modified right lobe graft, seven extended right lobe graft and five patients received left lateral graft. Median graft weight and mean graft to recipient weight ratio (GRWR) were 633.5 (IQR 473.5-633.5) grams and 1.23 (± 0.42), respectively. Most common biliary anastomosis was hepaticojejunostomy, done in 19 (73.1%) while duct to duct anastomosis was performed in 7 (26.9%) patients. Median follow-up was 96 (36-123) months. One patient had ulcerative colitis and none had cholangiocarcinoma. Two (7.7%) patients had bile leak during early post-transplant period. Three (11.1%) patients developed graft rejection and were managed successfully with steroid pulses. Three patients died during early post-transplant period while seven deaths occurred during long-term follow-up including one death due to COVID-19. Five (21.73%) patients had recurrence of PSC of which two patients had graft loss including one after retransplantation. The one year graft and patient survival rate was 88.5%. CONCLUSION: LDLT can be performed in PSC with good long-term outcomes with a risk of PSC recurrence in about one-fifth patients.

Computational study of novel inhibitory molecule, 1-(4-((2S,3S)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea, with high potential to competitively block ATP binding to the RNA dependent RNA polymerase of SARS-CoV-2 virus.

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive in silico screening for 16,776 potential molecules from recently established drug libraries based on two important pharmacophores (3-amino-4-phenylbutan-2-ol and piperazine). Based on initial assessment, 4042 molecules were obtained suitable as drug candidates, which were following Lipinski's rule. Molecular docking implemented for the analysis of molecular interactions narrowed this number of compounds down to 19. Subsequent to screening filtering criteria and considering the critical parameters viz. docking score and MM-GBSA binding free energy, 1-(4-((2S,3S)-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea (compound 1) was accomplished to score highest in comparison to the remaining 18 shortlisted drug candidates. Notably, compound 1 displayed higher docking score (-8.069 kcal/mol) and MM-GBSA binding free energy (-49.56 kcal/mol) than the control drug, remdesivir triphosphate, the active form of remdesivir as well as adenosine triphosphate. Furthermore, a molecular dynamics simulation was carried out (100 ns), which substantiated the candidacy of compound 1 as better inhibitor. Overall, our systematic in silico study predicts the potential of compound 1 to exhibit a more favourable specific activity than remdesivir triphosphate. Hence, we suggest compound 1 as a novel potential drug candidate, which should be considered for further exploration and validation of its potential against SARS-CoV-2 in wet lab experimental studies.Communicated by Ramasawamy H. Sarma.

Identification and structural studies of natural inhibitors against SARS-CoV-2 viral RNA methyltransferase (NSP16).

Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Marburg Virus- A threat during SARS-CoV-2 era: A Review.

In the German towns of Marburg, Frankfurt, and Belgrade in 1967, this single negative-stranded RNA virus was initially discovered. The importation of infected grivet monkeys from Uganda is what caused this virus-related sickness. As a result of the early link between viruses and non-human primates, this virus is frequently referred to as vervet monkey sickness. This virus causes Marburg hemorrhagic fever in humans and non-human primates. Human endothelial cells serve as the primary vehicle for replication. According to a 2009 report, the virus was being stored in Egyptian fruit bats (Rousettus aegyptiacus). Body fluids, unprotected sex, broken or injured skin, and other bodily fluids are the main routes of transmission. After the incubation period, symptoms like chills, headaches, myalgia, and stomach pain start to show up. There is no specific medication for such an infection, only hydration therapy and adequate oxygenation are followed. The following diagnostic techniques can be used to confirm the diagnosis: (i) an antibody-capture enzyme linked immunosorbent assay (ELISA); ii) an antigen capture ELISA test; iii) a serum neutralization test; iv) an RT PCR assay; v) electron microscopy; or vi) virus isolation by cell culture. Because MARV is a risk group 4 infection, laboratory staff must take strict precautions (RG-4).

Effect of Double Mutation (L452R and E484Q) on the Binding Affinity of Monoclonal Antibodies (mAbs) against the RBD-A Target for Vaccine Development.

The COVID-19 pandemic, caused by SARS-CoV-2, emerges as a global health problem, as the viral genome is evolving rapidly to form several variants. Advancement and progress in the development of effective vaccines and neutralizing monoclonal antibodies are promising to combat viral infections. In the current scenario, several lineages containing "co-mutations" in the receptor-binding domain (RBD) region of the spike (S) protein are imposing new challenges. Co-occurrence of some co-mutations includes delta (L452R/T478K), kappa (L452R/E484Q), and a common mutation in both beta and gamma variants (E484K/N501Y). The effect of co-mutants (L452R/E484Q) on human angiotensin-converting enzyme 2 (hACE2) binding has already been elucidated. Here, for the first time, we investigated the role of these RBD co-mutations (L452R/E484Q) on the binding affinity of mAbs by adopting molecular dynamics (MD) simulation and free-energy binding estimation. The results obtained from our study suggest that the structural and dynamic changes introduced by these co-mutations reduce the binding affinity of the viral S protein to monoclonal antibodies (mAbs). The structural changes imposed by L452R create a charged patch near the interfacial surface that alters the affinity towards mAbs. In E484Q mutation, polar negatively charged E484 helps in the formation of electrostatic interaction, while the neutrally charged Q residue affects the interaction by forming repulsive forces. MD simulations along with molecular mechanics-generalized Born surface area (MMGBSA) studies revealed that the REGN 10933, BD-368-2, and S2M11 complexes have reduced binding affinity towards the double-mutant RBD. This indicates that their mutant (MT) structures have a stronger ability to escape from most antibodies than the wild type (WT). However, EY6A Ab showed higher affinity towards the double MT-RBD complex as compared to the WT. However, no significant effect of the per-residue contribution of double-mutated residues was observed, as this mAb does not interact with the region harboring L452 and E484 residues.

Identification and characterization of aurintricarboxylic acid as a potential inhibitor of SARS-CoV-2 PLpro.

As the global health crisis due to evolution of mutations in SARS-CoV-2 continues, it is important to develop several effective antivirals to control the disease. Targeting papain-like protease (PLpro) of SARS-CoV-2 for drug development is a promising strategy due to its dual role in promoting viral replication and dysregulating host immune responses. Here, we screened a library of compounds to find potential inhibitors of PLpro. We find aurintricarboxylic acid (ATA) inhibits PLpro with Ki and IC50 values of 16 µM and 30 µM, respectively. The binding of ATA to PLpro was further characterized using isothermal titration calorimetry, differential scanning fluorimetry, dynamic light scattering and circular dichroism spectrometry. In vitro assays showed the antiviral potential of ATA with IC50 of 50 µM. In vivo efficacy was studied in Syrian hamsters and the results are being discussed.

Seroprevalence of severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies among health-care workers prior and after 4-6 weeks of coronavirus disease vaccine administration at tertiary care center of Southwest Bihar, India

AIM: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. To control the spread, a mass vaccination program is initiated. Antibody titer after vaccination can be a better marker to monitor immunological response. MATERIALS AND METHODS: The study was carried out at the Department of Microbiology, Narayan Medical College and Hospital, Jamuhar Sasaram, southwest Bihar, considering the sample size, type, and collection. First, antibody was tested before vaccination and second antibody value after 28 days of the first dose of COVID vaccine among the health-care workers and housekeeping staff. RESULTS: A total of 251 subjects were administered with vaccination (Covishield) to check the immunoglobulin g (IgG) responses. The concentration of the SARS-CoV-2 IgG antibody in female patients tended to be higher than in male patients. CONCLUSION: There is a difference in antibody positivity among males and females. Most of the participants had IgG positivity, because of their profession, vaccination boosted percentage positivity in both males and females. Females have more IgG levels compared to males. Hence, recommend that separate guidelines can be made between males and females for vaccination dosages. [ FROM AUTHOR] Copyright of Indian Journal of Health Sciences & Biomedical Research is the property of Wolters Kluwer India Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Genomic and structural mechanistic insight to reveal the differential infectivity of omicron and other variants of concern.

BACKGROUND: The genome of SARS-CoV-2, is mutating rapidly and continuously challenging the management and preventive measures adopted and recommended by healthcare agencies. The spike protein is the main antigenic site that binds to the host receptor hACE-2 and is recognised by antibodies. Hence, the mutations in this site were analysed to assess their role in differential infectivity of lineages having these mutations, rendering the characterisation of these lineages as variants of concern (VOC) and variants of interest (VOI). METHODS: In this work, we examined the genome sequence of SARS-CoV-2 VOCs and their phylogenetic relationships with the other PANGOLIN lineages. The mutational landscape of WHO characterized variants was determined and mutational diversity was compared amongst the different severity groups. We then computationally studied the structural impact of the mutations in receptor binding domain of the VOCs. The binding affinity was quantitatively determined by molecular dynamics simulations and free energy calculations. RESULTS: The mutational frequency, as well as phylogenetic distance, was maximum in the case of omicron followed by the delta variant. The maximum binding affinity was for delta variant followed by the Omicron variant. The increased binding affinity of delta strain followed by omicron as compared to other variants and wild type advocates high transmissibility and quick spread of these two variants and high severity of delta variant. CONCLUSION: This study delivers a foundation for discovering the improved binding knacks and structural features of SARS-CoV-2 variants to plan novel therapeutics and vaccine candidates against the virus.

Identification of a promising inhibitor from Illicium verum (star anise) against the main protease of SARS-CoV-2: insights from the computational study.

SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (Mpro) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has evaluated the potential of Illicium verum (star anise) phytoconstituents against Mpro by implementing a computational approach. We performed molecular docking and molecular dynamics simulation study with a set of 60 compounds to identify their potential to inhibit the main protease (Mpro) of SARS-CoV-2. DFT study and post dynamics free energy calculations were also performed to strengthen the findings. The identified four compounds by docking study exhibited the highest potential compared to other selected phytoconstituents. Further, density functional theory (DFT) calculation, molecular dynamics simulation and post dynamics MM-GBSA energy calculation predicted Verimol-G as a potential compound, which formed stable interactions through the catalytic dyad residues. The HOMO orbital energy (-0.250038) from DFT and the post dynamics binding free energy calculation (-73.33 Kcal/mol) correlate, suggesting Verimol-G is the best inhibitor compared to the other phytoconstituents. This compound also complies with the ADME properties of drug likeliness. Thus, based on a computational study, we suggest that Verimol G may be developed as a potential inhibitor against the main protease to combat COVID-19.Communicated by Ramaswamy H. Sarma.

Living donor liver transplant outcomes during the COVID-19 pandemic: does a decrease in case volume impact the overall outcomes?

Background: High-volume centers (HVCs) are classically associated with better outcomes. During the coronavirus disease 2019 (COVID-19) pandemic, there has been a decrease in the regular liver transplantation (LT) activity at our center. This study analyzed the effect of the decline in LT on posttransplant patient outcomes at our HVC. Methods: We compared the surgical outcomes of patients who underwent LT during the COVID-19 pandemic lockdown (April 1, 2020 to September 30, 2020) with outcomes in the pre-pandemic calendar year (April 1, 2019 to March 31, 2020). Results: During the 6 months of pandemic lockdown, 60 patients underwent LT (43 adults and 17 children) while 228 patients underwent LT (178 adults and 50 children) during the pre-pandemic calendar year. Patients in the pandemic group had significantly higher model for end-stage liver disease (MELD) scores (24.39±9.55 vs. 21.14±9.17, P=0.034), Child-Turcotte-Pugh scores (11.46±2.32 vs. 10.25±2.24, P=0.03), and incidence of acute-on-chronic liver failure (30.2% vs. 10.2%, P=0.002). Despite performing LT in sicker patients with COVID-19-related challenges, the 30-day (14% vs. 18.5%, P=0.479), 3-month (16.3% vs. 20.2%, P=0.557), and 6-month mortality rates (23.3% vs. 28.7%, P=0.477) were lower, but not statistically significant when compared to the pre-pandemic cohort. Conclusions: During the COVID-19 pandemic lockdown the number of LT procedures performed at our HVC declined by half because prevailing conditions allowed LT in very sick patients only. Despite these changes, outcomes were not inferior during the pandemic period compared to the pre-pandemic calendar year. Greater individualization of patient care contributed to non-inferior outcomes in these sick recipients.

Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses.

Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since millions of people are exposed to influenza virus and SARS-CoV-2, it is of great interest to develop a two-in-one vaccine that will be able to protect against infection of both viruses. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 RBD fused to GM-CSF as an adjuvant. GPI-RBD-GM-CSF fusion protein was expressed in CHO-S cells, purified and incorporated onto influenza VLPs to develop the hybrid vaccine. Our results show that the hybrid vaccine induced a strong antibody response and protected mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having significantly lower lung viral titers compared to naive mice. These results suggest that a hybrid vaccine strategy is a promising approach for developing multivalent vaccines to prevent influenza A and SARS-CoV-2 infections.

Differential Pathogenesis of SARS-CoV-2 Variants of Concern in Human ACE2-Expressing Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current pandemic, resulting in millions of deaths worldwide. Increasingly contagious variants of concern (VoC) have fueled recurring global infection waves. A major question is the relative severity of the disease caused by previous and currently circulating variants of SARS-CoV-2. In this study, we evaluated the pathogenesis of SARS-CoV-2 variants in human ACE-2-expressing (K18-hACE2) mice. Eight-week-old K18-hACE2 mice were inoculated intranasally with a representative virus from the original B.1 lineage or from the emerging B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), or B.1.1.529 (omicron) lineages. We also infected a group of mice with the mouse-adapted SARS-CoV-2 (MA10). Our results demonstrate that B.1.1.7, B.1.351 and B.1.617.2 viruses are significantly more lethal than the B.1 strain in K18-hACE2 mice. Infection with the B.1.1.7, B.1.351, and B.1.617.2 variants resulted in significantly higher virus titers in the lungs and brain of mice compared with the B.1 virus. Interestingly, mice infected with the B.1.1.529 variant exhibited less severe clinical signs and a high survival rate. We found that B.1.1.529 replication was significantly lower in the lungs and brain of infected mice in comparison with other VoC. The transcription levels of cytokines and chemokines in the lungs of B.1- and B.1.1.529-infected mice were significantly less when compared with those challenged with other VoC. Together, our data provide insights into the pathogenesis of previous and circulating SARS-CoV-2 VoC in mice.

Enablers for resilience and pandemic preparedness in food supply chain

The recent COVID-19 pandemic has caused enormous disruptions to supply chain (SCs). Border restrictions forced countless businesses to close either permanently or temporarily. However, the food industry is an essential sector that needs to be operational during a pandemic. Although the food industry has proactively worked towards fulfilling human needs, the food supply chain (FSC) faced numerous challenges, forcing SC managers to rethink their business strategy to cater to consumer demands effectively. In a pandemic situation, manufacturing operations need to repurpose and adapt to produce different high-demand products. Resilience initiatives help fight disruption phases in an uncertain environment by building capacity to resist and recover to a better position. This study identifies 14 key enablers to develop a resilient FSC and reveals the most significant enablers in India. We used a hybrid Delphi-interpretive structural modeling (ISM) and Fuzzy decision-making trial and evaluation laboratory (Fuzzy-DEMATEL) methodology to achieve these goals. The Delphi technique identified essential enablers, while the ISM analyzed the interrelationship among enablers and level of importance in a hierarchical structural model. Finally, the Fuzzy-DEMATEL categorized the enablers into the cause-effect group. This study helps SC decision-makers recognize the enablers and the contextual and causal relationships to improve resilience initiatives. It also helps them repurpose their manufacturing operations and shift to other highly required and high-demand production.

Differential Pathogenesis of SARS-CoV-2 Variants of Concern in Human ACE2-Expressing Mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the current pandemic, resulting in millions of deaths worldwide. Increasingly contagious variants of concern (VoC) have fueled recurring global infection waves. A major question is the relative severity of the disease caused by previous and currently circulating variants of SARS-CoV-2. In this study, we evaluated the pathogenesis of SARS-CoV-2 variants in human ACE-2-expressing (K18-hACE2) mice. Eight-week-old K18-hACE2 mice were inoculated intranasally with a representative virus from the original B.1 lineage or from the emerging B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), or B.1.1.529 (omicron) lineages. We also infected a group of mice with the mouse-adapted SARS-CoV-2 (MA10). Our results demonstrate that B.1.1.7, B.1.351 and B.1.617.2 viruses are significantly more lethal than the B.1 strain in K18-hACE2 mice. Infection with the B.1.1.7, B.1.351, and B.1.617.2 variants resulted in significantly higher virus titers in the lungs and brain of mice compared with the B.1 virus. Interestingly, mice infected with the B.1.1.529 variant exhibited less severe clinical signs and a high survival rate. We found that B.1.1.529 replication was significantly lower in the lungs and brain of infected mice in comparison with other VoC. The transcription levels of cytokines and chemokines in the lungs of B.1- and B.1.1.529-infected mice were significantly less when compared with those challenged with other VoC. Together, our data provide insights into the pathogenesis of previous and circulating SARS-CoV-2 VoC in mice.

Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study.

The recent emergence of pandemic of coronavirus (COVID-19) caused by SARS-CoV-2 has raised significant global health concerns. More importantly, there is no specific therapeutics currently available to combat against this deadly infection. The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is known to be essential for viral life cycle as it controls the coronavirus replication. 3CLpro could be a potential drug target as established before in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In the current study, we wanted to explore the potential of fused flavonoids as 3CLpro inhibitors. Fused flavonoids (5a,10a-dihydro-11H-benzofuro[3,2-b]chromene) are unexplored for their potential bioactivities due to their low natural occurrences. Their synthetic congeners are also rare due to unavailability of general synthetic methodology. Here we designed a simple strategy to synthesize 5a,10a-dihydro-11H-benzofuro[3,2-b]chromene skeleton and it's four novel derivatives. Our structural bioinformatics study clearly shows excellent potential of the synthesized compounds in comparison to experimentally validated inhibitor N3. Moreover, in-silico ADMET study displays excellent druggability and extremely low level of toxicity of the synthesized molecules. Further, for better understanding, the molecular dynamic approach was implemented to study the change in dynamicity after the compounds bind to the protein. A detailed investigation through clustering analysis and distance calculation gave us sound comprehensive data about their molecular interaction. In summary, we anticipate that the currently synthesized molecules could not only be a potential set of inhibitors against 3CLpro but also the insights acquired from the current study would be instrumental in further developing novel natural flavonoid based anti-COVID therapeutic spectrums.

SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways.

Transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) have been extensively used to investigate the pathogenesis and tissue tropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Neuroinvasion and the replication of SARS-CoV-2 within the central nervous system (CNS) of K18-hACE2 mice is associated with increased mortality; although, the mechanisms by which this occurs remain unclear. In this study, we generated primary neuronal cultures from K18-hACE2 mice to investigate the effects of a SARS-CoV-2 infection. We also evaluated the immunological response to SARS-CoV-2 infection in the CNS of K18-hACE2 mice and mouse neuronal cultures. Our data show that neuronal cultures obtained from K18-hACE2 mice are permissive to SARS-CoV-2 infection and support productive virus replication. Furthermore, SARS-CoV-2 infection upregulated the expression of genes involved in innate immunity and inflammation, including IFN-α, ISG-15, CXCL10, CCL2, IL-6 and TNF-α, in the neurons and mouse brains. In addition, we found that SARS-CoV-2 infection of neurons and mouse brains activates the ZBP1/pMLKL-regulated necroptosis pathway. Together, our data provide insights into the neuropathogenesis of SARS-CoV-2 infection in K18-hACE2 mice.

SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice.

The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared with the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1ß) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. In addition, robust expression of viral nucleocapsid protein and histopathological changes were detected in the lungs of B.1.351-infected mice. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.