Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

COVID-19 Vaccination in Pediatrics: Was It Valuable and Successful?

BACKGROUND: The mass vaccination of children against coronavirus 2019 disease (COVID-19) has been frequently debated. The risk-benefit assessment of COVID-19 vaccination versus infection in children has also been debated. AIM: This systematic review looked for answers to the question "was the vaccination of our children valuable and successful?". METHODS: The search strategy of different articles in the literature was based on medical subject headings. Screening and selection were based on inclusion/exclusion criteria. RESULTS AND DISCUSSION: The search results revealed that the majority of the reported adverse events after COVID-19 vaccination in pediatrics were mild to moderate, with few being severe. Injection site discomfort, fever, headache, cough, lethargy, and muscular aches and pains were the most prevalent side effects. Few clinical studies recorded significant side effects, although the majority of these adverse events had nothing to do with vaccination. In terms of efficacy, COVID-19 disease protection was achieved in 90-95% of cases for mRNA vaccines, in 50-80% of cases for inactivated vaccines, and in 58-92% of cases for adenoviral-based vaccines in children and adolescents. CONCLUSIONS: Based on available data, COVID-19 immunizations appear to be safe for children and adolescents. Furthermore, multiple studies have proven that different types of vaccines can provide excellent protection against COVID-19 in pediatric populations. The efficacy of vaccines against new SARS-CoV-2 variants and the reduction in vaccine-related long-term adverse events are crucial for risk-benefit and cost-effectiveness assessments; therefore, additional safety studies are required to confirm the long-term safety and effectiveness of vaccinations in children.

SARS-CoV-2 Variants Show a Gradual Declining Pathogenicity and Pro-Inflammatory Cytokine Stimulation, an Increasing Antigenic and Anti-Inflammatory Cytokine Induction, and Rising Structural Protein Instability: A Minimal Number Genome-Based Approach.

Hyper-transmissibility with decreased disease severity is a typical characteristic of the SARS-CoV-2 Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from December 15 to 31, 2021. We report that the pathogenicity of SARS-CoV-2 variants decreases in the order of Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order of Omicron > Gamma > Wuhan > Delta. The Omicron spike RBD shows lower pathogenicity but higher antigenicity than other variants. The reported decreased disease severity by the Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-γ and IL-4 induction efficacy. The mutations in the N protein are probably associated with this decreased IL-6 induction and human DDX21-mediated increased IL-4 production for Omicron. Due to the mutations, the stability of S, M, N, and E proteins decreases in the order of Omicron > Gamma > Delta > Wuhan. Although a stronger spike RBD-hACE2 binding of Omicron increases its transmissibility, the lowest stability of its spike protein makes spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally, the highest instability of the Omicron E protein may also be associated with decreased viral maturation and low viral load, leading to less severe disease and faster recovery. Our findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants. This minimal genome-based method may be used for other similar viruses avoiding robust analysis.

Can COVID-19 Vaccines Induce Premature Non-Communicable Diseases: Where Are We Heading to?

According to the WHO, as of January 2023, more than 850 million cases and over 6.6 million deaths from COVID-19 have been reported worldwide. Currently, the death rate has been reduced due to the decreased pathogenicity of new SARS-CoV-2 variants, but the major factor in the reduced death rates is the administration of more than 12.8 billion vaccine doses globally. While the COVID-19 vaccines are saving lives, serious side effects have been reported after vaccinations for several premature non-communicable diseases (NCDs). However, the reported adverse events are low in number. The scientific community must investigate the entire spectrum of COVID-19-vaccine-induced complications so that necessary safety measures can be taken, and current vaccines can be re-engineered to avoid or minimize their side effects. We describe in depth severe adverse events for premature metabolic, mental, and neurological disorders; cardiovascular, renal, and autoimmune diseases, and reproductive health issues detected after COVID-19 vaccinations and whether these are causal or incidental. In any case, it has become clear that the benefits of vaccinations outweigh the risks by a large margin. However, pre-existing conditions in vaccinated individuals need to be taken into account in the prevention and treatment of adverse events.

Impact of meteorological factors and population density on COVID-19 pandemic in Saudi Arabia.

Transmission and increase in cases and fatalities of coronavirus disease-2019 (COVID-19) are significantly influenced by the parameters of weather, human activities and population factors. However, study gap on the seasonality of COVID-19 and impact of environmental factors on the pandemic in Saudi Arabia is present. The main aim of the study is to evaluate the impact of environment on the COVID-19 pandemic. Data were analyzed from January 2020 to July 2021. The generalized estimating equation (GEE) was used to determine the effect of environmental variables on longitudinal outcomes. Spearman's rank correlation coefficient (rs ) was used to analyze the impact of different parameters on the outcome of the pandemic. Multiple sequence alignment was performed by using ClustalW. Vaccination and fatalities (r s = -0.85) had the highest association followed by vaccination with cases (r s = -0.81) and population density with the fatalities (rs  = 0.71). The growth rate had the highest correlation with sun hours (r s = -0.63). Isolates from variant of concern alpha and beta were detected. Most of the reference sequences in Saudi Arabia were closely related with B.1.427/429 variant. Clade GH (54%) was the most prevalent followed by O (27%), GR (9%), G (6%), and S (4%), respectively. Male to female patient ratio was 1.4:1. About 95% fatality and hospitalization were reported in patients aged >60 years. This study will create a comprehensive insight of the interaction of environmental factors and the pandemic and add knowledge on seasonality of COVID-19 in Saudi Arabia.

COVID-19 signalome: Potential therapeutic interventions.

The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development.

Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study.

Vitamin C, (ascorbic acid), vitamin D (cholecalciferol) and zinc (zinc sulfate monohydrate) supplements are important in immunity against coronavirus disease-2019 (COVID-19). However, a limited number of studies have been conducted on the association of vitamins and supplements with the reduced risks of COVID-19 infection. This study aims to evaluate the association of vitamins and supplements as treatment options to reduce the severity of COVID-19. Data were collected from 962 participants from 13 December 2020 to 4 February 2021. The presence of COVID-19 was confirmed by qRT-PCR. The Chi-square test and multivariate regression analyses were conducted. The ratio of uptake of vitamin C:vitamin D:zinc was 1:1:0.95. Uptake of vitamin C, vitamin D and zinc were significantly associated with the reduced risk of infection and severity of COVID-19 (OR: 0.006 (95% CI: 0.03-0.11) (p = 0.004)) and (OR: 0.03 (95% CI: 0.01-0.22) (p = 0.005)). The tendency of taking supplements was associated with the presence of infection of COVID-19 (p = 0.001), age (p = 0.02), sex (p = 0.05) and residence (p = 0.04). The duration of supplementation and medication was significantly associated with reduced hospitalization (p = 0.0001). Vitamins C, D and zinc were not significantly (p = 0.9) associated with a reduced risk of severity when taken through the diet. Hospitalization (p = 0.000001) and access to health facilities (p = 0.0097) were significantly associated with the survival period of the participants. Participants with better access to health facilities recovered early (OR: 6.21, 95% CI 1.56-24.7). This study will add knowledge in the field of treatment of COVID-19 by using vitamins and zinc supplements.

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde trafficking to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), which, in turn, acts as the assembly site for viral progeny. In infected cells, the newly synthesized S protein in endoplasmic reticulum (ER) is transported first to the Golgi body, and then from the Golgi body to the ERGIC compartment resulting in the formation of specific a motif at the C-terminal end. This review summarizes major events of SARS-CoV-2 infection route, immune response following host-cell infection as an important factor for disease outcome, as well as comorbidity issues of various tissues and organs arising due to COVID-19. Investigations on alterations of host-cell machinery and viral interactions with multiple intracellular signaling pathways could represent a major factor in more effective disease management.

Genomic surveillance, evolution and global transmission of SARS-CoV-2 during 2019-2022.

In spite of the availability of vaccine, the health burden associated with the COVID-19 pandemic continues to increase. An estimated 5 million people have died with SARS-CoV-2 infection. Analysis of evolution and genomic diversity can provide sufficient information to reduce the health burden of the pandemic. This study focused to conduct worldwide genomic surveillance. About 7.6 million genomic data were analyzed during 2019 to 2022. Multiple sequence alignment was conducted by using maximum likelihood method. Clade GK (52%) was the most predominant followed by GRY (12%), GRA (11%), GR (8%), GH (7%), G (6%), GV (3%), and O (1%), respectively. VOC Delta (66%) was the most prevalent variant followed by VOC Alpha (18%), VOC Omicron (13%), VOC Gamma (2%) and VOC Beta (1%), respectively. The frequency of point mutations including E484K, N501Y, N439K, and L452R at spike protein has increased 10%-92%. Evolutionary rate of the variants was 23.7 substitution per site per year. Substitution mutations E484K and N501Y had significant correlation with cases (r = .45, r = .23), fatalities (r = .15, r = .44) and growth rate R0 (r = .28, r = .54). This study will help to understand the genomic diversity, evolution and the impact of the variants on the outcome of the COVID-19 pandemic.

Multi-target potential of Indian phytochemicals against SARS-CoV-2: A docking, molecular dynamics and MM-GBSA approach extended to Omicron B.1.1.529.

BACKGROUND: SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. In recent times, phytochemicals have gained attention due to their therapeutic characteristics and are suggested as alternative and complementary treatments for infectious diseases. This present study aimed to identify potential inhibitors against reported protein targets of SARS-CoV-2. METHODOLOGY: We computationally investigated potential SARS-CoV-2 protein targets from the literature and collected druggable phytochemicals from Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Further, we implemented a systematic workflow of molecular docking, dynamic simulations and generalized born surface area free-energy calculations (MM-GBSA). RESULTS: Extensive literature search and assessment of 1508 articles identifies 13 potential SARS-CoV-2 protein targets. We screened 501 druggable phytochemicals with proven biological activities. Analysis of 6513(501 *13) docked phytochemicals complex, 26 were efficient against SARS-CoV-2. Amongst, 4,8-dihydroxysesamin and arboreal from Gmelina arborea were ranked potential against most of the targets with binding energy ranging between - 10.7 to - 8.2 kcal/mol. Additionally, comparative docking with known drugs such as arbidol (-6.6 to -5.1 kcal/mol), favipiravir (-5.5 to -4.5 kcal/mol), hydroxychloroquine (-6.5 to -5.1 kcal/mol), and remedesivir (-8.0 to -5.3 kcal/mol) revealed equal/less affinity than 4,8-dihydroxysesamin and arboreal. Interestingly, the nucleocapsid target was found commonly inhibited by 4,8-dihydroxysesamin and arboreal. Molecular dynamic simulation and Molecular mechanics generalized born surface area (MM-GBSA)calculations reflect that both the compounds possess high inhibiting potential against SARS-CoV-2 including the recently emerged Omicron variant (B.1.1.529). CONCLUSION: Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency.

Re-positive PCR of SARS-CoV-2 in health care persons during COVID-19 pandemic.

Reinfection rate with SARS-CoV-2 and degree of protection by the induced antibody after the first episode of the infection is not well known, so it makes a big dilemma for health care personnel (HCP) who work in the front line of combating SARS-CoV-2. In this study, we investigated the frequency of SARS-CoV-2 redetection among HCP after the initial onset of the infection in a children's hospital during one year. Out of 131 seropositive HCP, 13.7% of them were symptomatic and PCR positive during 74-360 days after first sampling. Analysis of demographic data of seropositive HCP showed a correlation between a higher number of family members, higher body mass index, and the existence of underlying diseases with SARS-CoV-2 redetection. In conclusion, reinfection is one of the important problems in the SARS-CoV-2 pandemic. Research on this topic can help us to find answers to questions for estimating the duration of human protection with produced immunity after the infection or vaccination.

Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2.

BACKGROUND: COVID-19 is an infectious disease declared as a global pandemic caused by SARS-CoV-2 virus. Genomic changes in the receptor binding domain (RBD) region of SARS-CoV-2 led to an increased, infectivity in humans through interaction with the angiotensin-converting enzyme2 (ACE2) receptor. Simultaneously, the genetic variants in ACE2 provide an opportunity for SARS-CoV-2 infection and severity. We demonstrate the binding efficiencies of RBDs of SARS-CoV-2 strain with ACE2 variants of the human host. METHODOLOGY: A Total of 615 SARS-CoV-2 genomes were retrieved from repository. Eighteen variations were identified contributing to structural changes in RBD that are distributed in 615 isolates. An analyses of 285 single nucleotide variances at the coding region of the ACE2 receptor showed 34 to be pathogenic. Homology models of 34 ACE2 and 18 RBD structures were constructed with 34 and 18 structural variants, respectively. Protein docking of 612 (34 *18) ACE2-RBD complexes showed variable affinities compared to wildtype Wuhan's and other SARS-CoV-2 RBDs, including Omicron B.1.1.529. Finally, molecular dynamic simulation was performed to determine the stability of the complexes. RESULTS: Among 612, the top 3 complexes showing least binding energy were selected. The ACE2 with rs961360700 variant showed the least binding energy (-895.2 Kcal/mol) on binding with the RBD of Phe160Ser variant compared to Wuhan's RBD complex. Interestingly, the binding energy of RBD of Omicron B.1.1.529 with ACE2 (rs961360700) structure showed least binding energy of -1010 Kcal/mol. Additionally, molecular dynamics showed structure stability for all the analysed complexes with the RMSD (0.22-0.26 nm), RMSF (0.11-0.13 nm), and Rg (2.53-2.56 nm). CONCLUSION: In conclusion, our investigation highlights the clinical variants contributing to structural variants in ACE2 receptors that lead to efficient binding of SARS-CoV-2. Therefore, screening of these ACE2 polymorphisms will help detect COVID-19 risk population so as to provide additional care and for safe management.

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach.

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (-8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (-8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins-the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.

Efficacy, Immunogenicity and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis.

There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of COVID-19 vaccines. Published phase I, phase II, and phase III trials analyzing safety and immunogenicity and phase III randomized clinical trials evaluating the efficacy of COVID-19 vaccines were included. We searched MEDLINE, Scopus, and The Lancet for published articles evaluating the relative reduction in COVID-19 risk after vaccination. Selected literatures were published between December 15, 2019 and May 15, 2021 on the safety, efficacy, and immunogenicity of COVID-19 vaccines. This meta-analysis included studies that confirmed cases of COVID-19 using reverse transcriptase polymerase chain reaction. This study detected 8,926 eligible research articles published on COVID-19 vaccines. Of these, 25 studies fulfilled the inclusion criteria. Among the selected articles, 19 randomized clinical trials, 2 non-randomized clinical trials, and 3 observational studies were analyzed. Seven (28%) studies were included in the meta-analysis. The efficacy of the adenovirus vector vaccine was 73% (95% CI = 69-77) and that of the messenger RNA (mRNA) vaccine was 85% (95% CI = 82-88) in participants aged ≥18 years. There are no reports of clinical trials in participants aged under 16 years. The production of neutralizing antibodies against receptor-binding domains (RBDs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in >90% of the vaccinated samples was reported within 0-30 days of the first or the second dose of the vaccine. Pain at the injection site was the most common local symptom in people receiving mRNA vaccines (29%-85% of participants). Fever (0.2%-95%) was the most prevalent in people receiving adenovirus vector vaccines, and fatigue (8.4%-55%) was the most common side effect in people receiving the mRNA vaccines. Studies suggest that mRNA vaccines and adenovirus vector vaccines can provide moderate to high protection against COVID-19 infection in people over 18 years. Evidence of the long-term protection of the vaccines in people aged under 16 years against the multiple variants of COVID-19 are limited. This study will provide an integrated evaluation on the efficacy, safety, and immunogenicity of the COVID-19 vaccines.

Protective measures are associated with the reduction of transmission of COVID-19 in Bangladesh: A nationwide cross-sectional study.

Coronavirus disease 2019 (COVID-19) pandemic has become a major public health issue globally. Preventive health measures against COVID-19 can reduce the health burden significantly by containing the transmission. A few research have been undertaken on the effectiveness of preventive strategies such as mask use, hand washing, and keeping social distance in preventing COVID-19 transmission. The main aim of this study was to determine the association of the preventive measures with the reduction of transmission of COVID-19 among people. Data was collected during January 06, 2021 to May 10, 2021 from 1690 participants in Bangladesh. A validated questionnaire was used to collect both the online and offline data. Chi-square test and logistic regression analyses were performed to determine the association among the variables. The prevalence of COVID-19 was 11.5% (195 of 1690) among the population. Age, gender, occupation and monthly income of the participants were significantly associated with the likelihood of following the preventive measures. The risk of infection and death reduced significantly among the participants following preventive measures (p = .001). The odds of incidence was lower among the participants using masks properly (OR: 0.02, 95% CI: 0.01-0.43), maintaining social distances (OR: 0.04, 95% CI: 0.01-0.33), avoiding crowded places (OR: 0.07, 95% CI: 0.02-0.19) and hand shaking (OR: 0.17, 95% CI: 0.09-0.41). This study suggests that preventive health measures are significantly associated with the reduction of the risk of infection of COVID-19. Findings from this study will help the policymakers to take appropriate steps to curb the health burden of COVID-19.

Niclosamide for Covid-19: bridging the gap.

AIM/PURPOSE: Niclosamide (NCL) is an anthelminthic drug, which is widely used to treat various diseases due to its pleiotropic anti-inflammatory and antiviral activities. NCL modulates of uncoupling oxidative phosphorylation and different signaling pathways in human biological processes. The wide-spectrum antiviral effect of NCL makes it a possible candidate for recent pandemic SARS-CoV-2 infection and may reduce Covid-19 severity. Therefore, the aim of the present study was to review and clarify the potential role of NCL in Covid-19. METHODS: This study reviewed and highlighted the protective role of NCL therapy in Covid-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. RESULTS: NCL has noteworthy anti-inflammatory and antiviral effects. The primary antiviral mechanism of NCL is through neutralization of endosomal PH and inhibition of viral protein maturation. NCL acts as a proton carrier, inhibits homeostasis of endosomal PH, which limiting of viral proliferation and release. The anti-inflammatory effects of NCL are mediated by suppression of inflammatory signaling pathways and release of pro-inflammatory cytokines. However, the major limitation in using NCL is low aqueous solubility, which reduces oral bioavailability and therapeutic serum concentration that reducing the in vivo effect of NCL against SARS-CoV-2. CONCLUSIONS: NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.

Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas.

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting "PVQLSY" motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 Mpro, NSP7, NSP10, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders.

The potential role of neopterin in Covid-19: a new perspective.

Neopterin (NPT) is a member of pteridines group, synthesized by macrophages when stimulated by interferon gamma (INF-γ). NPT is regarded as a macrophage stimulation indicator, marker of cellular immune activation and T helper 1 (Th1) type 1 immune response. Here, we aimed to provide a view point on the NPT features and role in Covid-19. Serum NPT level is regarded as an independent prognostic factor for Covid-19 severity, with levels starting to increase from the 3rd day of SARS-CoV-2 infection, being associated with severe dyspnea, longer hospitalization period and complications. Also, early raise of NPT reflects monocytes/macrophages activation before antibody immune response, despite the NPT level may also remain high in Covid-19 patients or at the end of incubation period before the onset of clinical symptoms. On the other hand, NPT attenuates the activity of macrophage foam cells and is linked to endothelial inflammation through inhibition of adhesion molecules and monocytes migration. However, NPT also exerts anti-inflammatory and antioxidant effects by suppressing NF-κB signaling and NLRP3 inflammasomes. NPT can be viewed as a protective compensatory mechanism to counterpoise hyper-inflammation, oxidative stress, and associated organ damage.

The Spike of SARS-CoV-2: Uniqueness and Applications.

The Spike (S) protein of the SARS-CoV-2 virus is critical for its ability to attach and fuse into the host cells, leading to infection, and transmission. In this review, we have initially performed a meta-analysis of keywords associated with the S protein to frame the outline of important research findings and directions related to it. Based on this outline, we have reviewed the structure, uniqueness, and origin of the S protein of SARS-CoV-2. Furthermore, the interactions of the Spike protein with host and its implications in COVID-19 pathogenesis, as well as drug and vaccine development, are discussed. We have also summarized the recent advances in detection methods using S protein-based RT-PCR, ELISA, point-of-care lateral flow immunoassay, and graphene-based field-effect transistor (FET) biosensors. Finally, we have also discussed the emerging Spike mutants and the efficacy of the Spike-based vaccines against those strains. Overall, we have covered most of the recent advances on the SARS-CoV-2 Spike protein and its possible implications in countering this virus.