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The large-scale real-time sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes has allowed for rapid identification of concerning variants through phylogenetic analysis. However, the nature of phylogenetic reconstruction is typically static, in that the relationships between taxonomic units, once defined, are not subject to alterations. Furthermore, most phylogenetic methods are intrinsically batch mode in nature, requiring the presence of the entire data set. Finally, the emphasis of phylogenetics is on relating taxonomical units. These characteristics complicate the application of classical phylogenetics methods to represent relationships in molecular data collected from rapidly evolving strains of an etiological agent, such as SARS-CoV-2, since the molecular landscape is updated continuously as samples are collected. In such settings, variant definitions are subject to epistemological constraints and may change as data accumulate. Furthermore, representing within-variant molecular relationships may be as important as representing between variant relationships. This article describes a novel data representation framework called dynamic epidemiological networks (DENs) along with algorithms that underpin its construction to address these issues. The proposed representation is applied to study the molecular development underlying the spread of the COVID-19 (coronavirus disease 2019) pandemic in two countries: Israel and Portugal spanning a 2-year period from February 2020 to April 2022. The results demonstrate how this framework could be used to provide a multiscale representation of the data by capturing molecular relationships between samples as well as those between variants, automatically identifying the emergence of high frequency variants (lineages), including variants of concern such as Alpha and Delta, and tracking their growth. Additionally, we show how analyzing the evolution of the DEN can help identify changes in the viral population that could not be readily inferred from phylogenetic analysis.

Background: The clinical profile and course of COVID-19 evolved perilously in a second wave, leading to the use of various treatment modalities that included homeopathy. This prognostic factor research (PFR) study aimed to identify clinically useful homeopathic medicines in this second wave., Methods: This was a retrospective, multi-centred observational study performed from March 2021 to May 2021 on confirmed COVID-19 cases who were either in home isolation or at COVID Care Centres in Delhi, India. The data were collected from integrated COVID Care Centres where homeopathic medicines were prescribed along with conventional treatment. Only those cases that met a set of selection criteria were considered for analysis. The likelihood ratio (LR) was calculated for the frequently occurring symptoms of the prescribed medicines. An LR of 1.3 or greater was considered meaningful., Results: Out of 769 confirmed COVID-19 cases reported, 514 cases were selected for analysis, including 467 in home isolation. The most common complaints were cough, fever, myalgia, sore throat, loss of taste and/or smell, and anxiety. Most cases improved and there was no adverse reaction. Certain new symptoms, e.g., headache, dryness of mouth and conjunctivitis, were also seen. Thirty-nine medicines were prescribed, the most frequent being Bryonia alba followed by Arsenicum album , Pulsatilla nigricans , Belladonna , Gelsemium sempervirens , Hepar sulphuris , Phosphorus , Rhus toxicodendron and Mercurius solubilis . By calculating LR, the prescribing indications of these nine medicines were ascertained., Conclusion: Add-on use of homeopathic medicines has shown encouraging results in the second wave of COVID-19 in integrated care facilities. Further COVID-related research is required to be undertaken on the most commonly prescribed medicines., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

The quick widespread of the coronavirus and speedy upsurge in the tally of cases demand the fast development of effective drugs. The uridine-directed endoribonuclease activity of nonstructural protein 15 (Nsp15) of the coronavirus is responsible for the invasion of the host immune system. Therefore, developing potential inhibitors against Nsp15 is a promising strategy. In this concern, the in silico approach can play a significant role, as it is fast and cost-effective in comparison to the trial and error approaches of experimental investigations. In this study, six turmeric derivatives (curcuminoids) were chosen for in silico analysis. The molecular interactions, pharmacokinetics, and drug-likeness of all the curcuminoids were measured. Further, the stability of Nsp15-curcuminoids complexes was appraised by employing molecular dynamics (MD) simulations and MM-PBSA approaches. All the molecules were affirmed to have strong interactions and pharmacokinetic profile. The MD simulations data stated that the Nsp15-curcuminoids complexes were stable during simulations. All the curcuminoids showed stable and high binding affinity, and these curcuminoids could be admitted as potential modulators for Nsp15 inhibition., (© 2022 John Wiley & Sons Ltd.)

Scrub typhus is an under diagnosed re-emerging vector borne disease caused by an intracellular gram negative bacteria, Orientia. The disease is commonly prevalent in rural and hilly areas of Tsutsugumashi triangle. The diagnosis of the disease is very challenging due to similarity of its early symptoms with other febrile illnesses, like dengue and COVID 19, as well as non-availability of rapid, reliable and cost-effective methods. Moreover, the diverse clinical presentation in severe cases make it significant health problem. The occupational and behavioral risks responsible for the transmission lead to urgent need of vaccine development against the disease. The complete knowledge about its pathogenesis and the interaction with host's immune cells may help the scientists in developing the appropriate diagnostic methods as well as the vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Prognostic factor research (PFR), prevalence of symptoms and likelihood ratio (LR) play an important role in identifying prescribing indications of useful homeopathic remedies. It involves meticulous unbiased collection and analysis of data collected during clinical practice. This paper is an attempt to identify causes of bias and suggests ways to mitigate them for improving the accuracy in prescribing for better clinical outcomes and execution of randomized controlled studies., Methods: A prospective, open label, observational study was performed from April 2020 to December 2020 at two COVID Health Centers. A custom-made Excel spreadsheet containing 71 fields covering a spectrum of COVID-19 symptoms was shared with doctors for regular reporting. Cases suitable for PFR were selected. LR was calculated for commonly occurring symptoms. Outlier values with LR ≥5 were identified and variance of LRs was calculated., Results: Out of 1,889 treated cases of confirmed COVID-19, 1,445 cases were selected for pre-specified reasons. Nine medicines, Arsenicum album, Bryonia alba, Gelsemium sempervirens, Pulsatilla nigricans, Hepar sulphuricus, Magnesia muriaticum, Phosphorus, Nux vomica and Belladonna , were most frequently prescribed. Outlier values and large variance for Hepar sulphuricus and Magnesia muriaticum were noticed as indication of bias. Confirmation bias leading to lowering of symptom threshold, keynote prescribing, and deficiency in checking of all symptoms in each case were identified as the most important sources of bias., Conclusion: Careful identification of biases and remedial steps such as training of doctors, regular monitoring of data, checking of all pre-defined symptoms, and multicenter data collection are important steps to mitigate biases., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Currently, there are no particular antivirals available to battle with COVID-19. The RNA-dependent RNA polymerase (RdRp) has emerged as a novel drug target due to its essential role in virus replication. In this study, turmeric-derived compounds were chosen and subjected to in-silico analysis to evaluate their binding affinity against the RdRp-RNA complex of SARS-CoV-2. Our in-silico approach included the analysis of protein-ligand interactions by molecular docking and molecular dynamics simulations, followed by free energy calculations by molecular mechanics Poisson-Boltzmann surface area analysis. Curcumin and diacetylcurcumin showed stability and good binding affinity at the active site of the SARS-CoV-2 RdRp-RNA complex. Furthermore, to validate the potency of selected compounds, we compared them with Favipiravir and Remdesivir antiviral drugs from our previous analysis on targeting tea bioactive molecules to inhibit RdRp-RNA complex. The comparative analysis revealed that the selected compounds showed higher potential to be developed as RdRp-RNA inhibitors than antiviral medicines Remdesivir and Favipiravir. However, these compounds need to be further validated by in-vitro and in-vivo investigations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Current approaches for oral health care rely on procedures that are unaffordable to impoverished populations, whereas aerosolized droplets in the dental clinic and poor oral hygiene may contribute to spread of several infectious diseases including COVID-19, requiring new solutions for dental biofilm/plaque treatment at home. Plant cells have been used to produce monoclonal antibodies or antimicrobial peptides for topical applications to decrease colonization of pathogenic microbes on dental surface. Therefore, we investigated an affordable method for dental biofilm disruption by expressing lipase, dextranase or mutanase in plant cells via the chloroplast genome. Antibiotic resistance gene used to engineer foreign genes into the chloroplast genome were subsequently removed using direct repeats flanking the aadA gene and enzymes were successfully expressed in marker-free lettuce transplastomic lines. Equivalent enzyme units of plant-derived lipase performed better than purified commercial enzymes against biofilms, specifically targeting fungal hyphae formation. Combination of lipase with dextranase and mutanase suppressed biofilm development by degrading the biofilm matrix, with concomitant reduction of bacterial and fungal accumulation. In chewing gum tablets formulated with freeze-dried plant cells, expressed protein was stable up to 3 years at ambient temperature and was efficiently released in a time-dependent manner using a mechanical chewing simulator device. Development of edible plant cells expressing enzymes eliminates the need for purification and cold-chain transportation, providing a potential translatable therapeutic approach. Biofilm disruption through plant enzymes and chewing gum-based delivery offers an effective and affordable dental biofilm control at home particularly for populations with minimal oral care access., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause ˜17% of all human deaths and their management and control places an immense burden on healthcare systems worldwide. Traditional approaches for the prevention and control of infectious diseases include vaccination programmes, hygiene measures and drugs that suppress the pathogen, treat the disease symptoms or attenuate aggressive reactions of the host immune system. The provision of vaccines and biologic drugs such as antibodies is hampered by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, particularly in developing countries where infectious diseases are prevalent and poorly controlled. Molecular farming, which uses plants for protein expression, is a promising strategy to address the drawbacks of current manufacturing platforms. In this review article, we consider the potential of molecular farming to address healthcare demands for the most prevalent and important epidemic and pandemic diseases, focussing on recent outbreaks of high-mortality coronavirus infections and diseases that disproportionately affect the developing world., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is the causative agent of Corona Virus Disease 2019 (COVID-19). Lower production of type I and III interferons and higher levels of inflammatory mediators upon SARS-CoV2 infection contribute to COVID-19 pathogenesis. Optimal interferon production and controlled inflammation are essential to limit COVID-19 pathogenesis. However, the aggravated inflammatory response observed in COVID-19 patients causes severe damage to the host and frequently advances to acute respiratory distress syndrome (ARDS). Toll-like receptor 7 and 8 (TLR7/8) signaling pathways play a central role in regulating induction of interferons (IFNs) and inflammatory mediators in dendritic cells. Controlled inflammation is possible through regulation of TLR mediated response without influencing interferon production to reduce COVID-19 pathogenesis. This review focuses on inflammatory mediators that contribute to pathogenic effects and the role of TLR pathways in the induction of interferon and inflammatory mediators and their contribution to COVID-19 pathogenesis. We conclude that potential TLR7/8 agonists inducing antiviral interferon response and controlling inflammation are important therapeutic options to effectively eliminate SARS-CoV2 induced pathogenesis. Ongoing and future studies may provide additional evidence on their safety and efficacy to treat COVID-19 pathogenesis., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The Spike receptor binding domain (S-RBD) from SARS-CoV-2, a crucial protein for the entrance of the virus into target cells is known to cause infection by binding to a cell surface protein. Hence, reckoning therapeutics for the S-RBD of SARS-CoV-2 may address a significant way to target viral entry into the host cells. Herein, through in-silico approaches (Molecular docking, molecular dynamics (MD) simulations, and end-state thermodynamics), we aimed to screen natural molecules from different plants for their ability to inhibit S-RBD of SARS-CoV-2. We prioritized the best interacting molecules (Diacetylcurcumin and Dicaffeoylquinic acid) by analysis of protein-ligand interactions and subjected them for long-term MD simulations. We found that Dicaffeoylquinic acid interacted prominently with essential residues (Lys417, Gln493, Tyr489, Phe456, Tyr473, and Glu484) of S-RBD. These residues are involved in interactions between S-RBD and ACE2 and could inhibit the viral entry into the host cells. The in-silico analyses indicated that Dicaffeoylquinic acid and Diacetylcurcumin might have the potential to act as inhibitors of SARS-CoV-2 S-RBD. The present study warrants further in-vitro and in-vivo studies of Dicaffeoylquinic acid and Diacetylcurcumin for validation and acceptance of their inhibitory potential against S-RBD of SARS-CoV-2., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Influenza infection is associated with an increased risk of cardiovascular events (myocardial infarction, stroke, and heart failure exacerbation) and mortality, and all-cause mortality in patients with CVD. Infection with influenza leads to a systemic inflammatory and thrombogenic response in the host body, which further causes destabilization of atherosclerotic plaques. Influenza vaccination has been shown to be protective against cardiovascular and cerebrovascular events in several observational and prospective studies of at-risk populations. Hence, many international guidelines recommend influenza vaccination for adults of all ages, especially for individuals with high-risk conditions such as CVD. Despite these long-standing recommendations, influenza vaccine uptake among US adults with CVD remains suboptimal. Specifically, vaccination uptake is strikingly low among patients aged <65 years, non-Hispanic Black individuals, those without health insurance, and those with diminished access to healthcare services. Behavioral factors such as perceived vaccine efficacy, vaccine safety, and attitudes towards vaccination play an important role in vaccine acceptance at the individual and community levels. With the ongoing COVID-19 pandemic, there is a potential threat of a concurrent epidemic with influenza. This would be devastating for vulnerable populations such as adults with CVD, further stressing the need for ensuring adequate influenza vaccination coverage. In this review, we describe a variety of strategies to improve the uptake of influenza vaccination in patients with CVD through improved understanding of key sociodemographic determinants and behaviors that are associated with vaccination, or the lack thereof. We further discuss the potential use of relevant strategies for COVID-19 vaccine uptake among those with CVD.

Objective: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a severe immune-mediated disorder. We aim to report the neurologic features of children with PIMS-TS., Methods: We identified children presenting to a large children's hospital with PIMS-TS from March to June 2020 and performed a retrospective medical note review, identifying clinical and investigative features alongside short-term outcome of children presenting with neurologic symptoms., Results: Seventy-five patients with PIMS-TS were identified, 9 (12%) had neurologic involvement: altered conciseness (3), behavioral changes (3), focal neurology deficits (2), persistent headaches (2), hallucinations (2), excessive sleepiness (1), and new-onset focal seizures (1). Four patients had cranial images abnormalities. At 3-month follow-up, 1 child had died, 1 had hemiparesis, 3 had behavioral changes, and 4 completely recovered. Systemic inflammatory and prothrombotic markers were higher in patients with neurologic involvement (mean highest CRP 267 vs 202 mg/L, p = 0.05; procalcitonin 30.65 vs 13.11 μg/L, p = 0.04; fibrinogen 7.04 vs 6.17 g/L, p = 0.07; d-dimers 19.68 vs 7.35 mg/L, p = 0.005). Among patients with neurologic involvement, these markers were higher in those without full recovery at 3 months (ferritin 2284 vs 283 μg/L, p = 0.05; d-dimers 30.34 vs 6.37 mg/L, p = 0.04). Patients with and without neurologic involvement shared similar risk factors for PIMS-TS (Black, Asian and Minority Ethnic ethnicity 78% vs 70%, obese/overweight 56% vs 42%)., Conclusions: Broad neurologic features were found in 12% patients with PIMS-TS. By 3-month follow-up, half of these surviving children had recovered fully without neurologic impairment. Significantly higher systemic inflammatory markers were identified in children with neurologic involvement and in those who had not recovered fully., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause ˜17% of all human deaths and their management and control places an immense burden on healthcare systems worldwide. Traditional approaches for the prevention and control of infectious diseases include vaccination programmes, hygiene measures and drugs that suppress the pathogen, treat the disease symptoms or attenuate aggressive reactions of the host immune system. The provision of vaccines and biologic drugs such as antibodies is hampered by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, particularly in developing countries where infectious diseases are prevalent and poorly controlled. Molecular farming, which uses plants for protein expression, is a promising strategy to address the drawbacks of current manufacturing platforms. In this review article, we consider the potential of molecular farming to address healthcare demands for the most prevalent and important epidemic and pandemic diseases, focussing on recent outbreaks of high-mortality coronavirus infections and diseases that disproportionately affect the developing world.

For the last three years, the world has faced the unexpected spread of the pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The high mortality rate and ever-changing shape of the virus are the challenging factors in the effective management of SARS-CoV-2. However, in last three years, research communities have made significant progress in developing vaccines and controlling the spread of the pandemic to a certain extent. These vaccines contain the attenuated pathogens, which after application did not kill the virus but protected the human by enhancing the immune system response during pandemic exposure. However, the negative side effects and the high cost of the synthetic vaccines are always of concern for researchers, consumers, and the government. Therefore, as an alternative to synthetic drugs, natural medicines or natural plant products have piqued researchers' interest. Algae are considered as a treasure house of bioactive compounds such as carotenoids, vitamins, polysaccharides, proteins, etc. These bioactive compounds have been well documented for the treatments of various human ailments such as cancer and cardiovascular diseases. Furthermore, sulfated polysaccharides such as alginate and carrageenan have been reported as having antiviral and immunomodulating properties. Therefore, this review addresses algal polysaccharides, especially alginate and carrageenan, and their application in the treatment of COVID-19. In addition, in silico approaches are discussed for the inhibition of the S1-RBD (receptor-binding domain) of SARS-CoV-2, which attaches to the host receptor ACE2 (angiotensin-converting enzyme 2), and the interaction with the network of relative proteins is also explored, which will help in drug discovery and drug design. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Binding of linoleic acid (LA) to the spike trimer stabilizes it in closed conformation hindering its binding to angiotensin-converting enzyme-2, thus decreasing infectivity. In the current study, we tend to repurpose Food and Drug Administration-approved drugs as binder to the LA binding pocket in wild and double mutant spike protein. MATERIALS AND METHODS: Approved drugs from DrugBank database (n = 2456) were prepared using Ligprep module of Schrodinger. Crystal structure of LA bound to spike trimer was retrieved (PDB: 6ZB4) and prepared using protein preparation wizard and grid was generated. A virtual screening was performed. With the help of molecular dynamics (MD) studies interaction profile of screened drugs were further evaluated. The selected hits were further evaluated for binding to the double mutant form of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). RESULTS AND DISCUSSION: Following virtual screening, a total of 26 molecules were shortlisted, which were further evaluated using 1ns MD simulation study. Four ligands showing better root mean square deviation (RMSD), RMSD to LA with interaction profile similar to LA were further evaluated using 100 ns MD simulation studies. A total of 2 hits were identified, which performed better than LA (selexipag and pralatrexate). Both these ligands were also found to bind to LA binding site of the double mutant form (E484Q and L452R); however, the binding affinity of pralatrexate was found to be better. CONCLUSION: We have identified 2 ligands (selexipag and pralatrexate) as possible stable binders to the LA binding site in spike trimer (wild and mutant form). Among them, pralatrexate has shown in vitro activity against SARS-CoV-2, validating our study results. [ABSTRACT FROM AUTHOR]

Background/Objective  During the coronavirus disease 2019 (COVID-19) pandemic, several homeopathic prognostic factor research (PFR) projects have been undertaken. We found two projects with comparable outcomes to assess consistency and possible flaws. Methods  Two comparisons were made. (1) Outcome of a PFR data collection from the Liga Medicorum Homoeopathica Internationalis (LMHI) by about 100 doctors with 541 cases was compared with a previous analysis of 161 cases in the same database. (2) The updated LMHI database was also compared with a data collection carried out in India by four doctors with a total of 1,445 cases. Differences that resulted in conflicting outcomes (indication in one, contraindication in the other) were examined for possible causes. Results  There was only a single outcome in the updated LMHI database that conflicted with the previous dataset, and this could have been due to statistical variation. The Indian data contained many cases, from few doctors, while the LMHI database had few cases per doctor, but many doctors. The overlap between the projects (individual cases entered in both) was between zero and 22%. In 72 comparisons we found six (8.3%) conflicting outcomes. Possible causes were statistical error due to small numbers of cases and/or observers, confirmation bias, and keynote prescribing if this resulted in symptoms being inadequately checked. Conclusion  There was little conflict between the outcomes of the two versions of one project and between the two different PFR projects. Differences could mostly be explained by causes that can be managed. This consistency should primarily be interpreted as showing a strong overall consensus between homeopathic practitioners worldwide, but with variation of consensus between small groups of practitioners. [ABSTRACT FROM AUTHOR]

An epidemiological study was conducted for investigation of bovine coronavirus by antigen Enzyme-linked immunosorbent assay kit in dairy calves from Central India (Madhya Pradesh and Chhattisgarh states) and North India (Uttar Pradesh state). Different epidemiological parameters like age, parity, colour and consistency of faecal materials and seasonal changes in a year were recorded. A total of 816 faecal samples were screened and out of which 7 (0.85%) animals were found to be positive for bovine coronavirus. The higher prevalence was recorded in north India followed by central India. Age wise higher prevalence was recorded below 2 month calves. Seasonally, the prevalence of coronavirus infection was higher in monsoon season and in first parity of calves as compared to other season and parity. Prevalence of coronavirus infection was higher in watery diarrhoea faecal materials than pasty yellow colour diarrhoea. The observations of the present study would provide the basis for further an effective explorative surveillance and epidemiological studies to know the real impact of coronavirus infection with associated risk factors in dairy calves of India. [ABSTRACT FROM AUTHOR]

Traditional Indian medical practices (Ayurveda, Siddha, Unani, and homeopathy) are a vast reservoir of knowledge about medicinal plants. The promising pharmacological properties of these plants have paved the way for developing therapy against novel Coronavirus (CoV) infection. The current review will summarize published works of literature on the effects of traditional Indian medicinal plants against acute respiratory infection (COVID‐19, SARS, Influenza, and Respiratory syncytial virus infection) and registered clinical trials of traditional Indian herbal medicines in COVID‐19. The current study aims to comprehensively evaluate the data of traditional Indian medicinal plants to warrant their use in COVID‐19 management. PubMed, Embase, and Cochrane databases were searched along with different clinical trial databases. A total of 22 relevant traditional Indian medicinal plants (35 relevant studies) were included in the current study having potential antiviral properties against virus‐induced respiratory illness along with promising immunomodulatory and thrombolytic properties. Further, 36 randomized and nonrandomized registered clinical trials were also included that were aimed at evaluating the efficacy of herbal plants or their formulations in COVID‐19 management. The antiviral, immunomodulatory, and thrombolytic activities of the traditional Indian medicinal plants laid down a strong rationale for their use in developing therapies against SARS‐CoV‐2 infection. The study identified some important potential traditional Indian medicinal herbs such as Ocimum tenuiflorum, Tinospora cordifolia, Achyranthes bidentata, Cinnamomum cassia, Cydonia oblonga, Embelin ribes, Justicia adhatoda, Momordica charantia, Withania somnifera, Zingiber officinale, Camphor, and Kabusura kudineer, which could be used in therapeutic strategies against SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Objectives  The aim of the study is to determine the magnitude of repercussions of coronavirus disease 2019 (COVID-19) pandemic on neurosurgical specialty and formulate a management approach. Materials and Methods  This combined retrospective and prospective study was done in neurosurgical specialty of IMS–BHU, Varanasi, India, a tertiary care center, between January 1, 2020 and May 31, 2020. Analysis of impact on neurosurgical emergency and electives was done over before pandemic, during lockdown 1 and 2 and during lockdown 3 and 4 timelines. Effects of COVID-19 pandemic on psychology of neurosurgical team (50 members) and on patient party (88) were also evaluated. Virtual learning and webinars as a substitute to residential neurosurgical training were analyzed by a questionnaire given to 13 neurosurgeons of our department. Statistical Analysis  Ordinary one-way ANOVA (analysis of variance) and unpaired t -test were used according to data analyzed. p < 0.05 was considered statistically significant. GraphPad Prism software was used for this analysis. Results  On an average 8.22 admissions per day were done in neurosurgical emergency before pandemic. After lockdown these figures reduced to 3.2 admissions per day during lockdown 1 and 2 and to 5.36 admissions per day during lockdown 3 and 4. There was significant reduction in neurotrauma admission rate during lockdown (p < 0.0001) at our center. There was 76% reduction in emergency neurosurgical operated cases during pandemic. There was significant reduction in outpatient department (OPD) attendance per day, OPD admissions per day (p < 0.0001), and total elective surgeries (p < 0.0001) during lockdown. Of 50 neurosurgical team members (neurosurgeons, nursing, and ground staff) interviewed, 90% of them had the fear of contacting the COVID-19 disease, fear of well-being of family and children, and difficulty in transport. Three out of 13 neurosurgeons (23.1%) agreed on change in practice based on what they learned from virtual teaching and webinars and only two of them (15.4%) accepted improvement of skills based on virtual learning. Conclusion  The COVID-19 pandemic is causing a significant impact on health care systems worldwide. For conserving resources elective surgical procedures should be limited. This pandemic has a negative impact on neurosurgical resident training program and psychology of both neurosurgical unit and patients. [ABSTRACT FROM AUTHOR]

Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta‐analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta‐analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure," "virological cure," "death or clinical worsening of disease," "radiological progression," and safety. RevMan was used for meta‐analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in "time to body temperature normalization" and one study reported less "cough days" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11‐0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13‐44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37‐21.97), and safety (OR, 2.19, 95% CI, 0.59‐8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion. Research Highlights: Following the demonstration of the efficacy of hydroxychloroquine (HCQ) against severe acute respiratory syndrome coronavirus 2 in vitro, many trials were started to evaluate its efficacy in clinical settings.However, no systematic review and meta‐analysis have addressed the issue to the safety and efficacy of HCQ in coronavirus disease 2019 (COVID‐19).We searched 16 literature databases finally seven articles were identified, which evaluated the therapeutic efficacy of HCQ either alone or in combination with azithromycin in COVID‐19.RevMan was used for meta‐analysis. For continuous outcome, mean difference and for a dichotomous outcome, odds ratio with 95% confidence interval was calculated. Model selection (fixed effect or random effect) was done on the basis of heterogeneity among different studies.Three studies reported the safety and efficacy of HCQ vs control/conventional treatment in terms of safety and efficacy in COVID‐19.Treatment with HCQ resulted in benefit in terms of less number of cases with radiological progression with no increase in adverse events when compared with control/conventional/standard treatment.We can also expect a benefit in terms of a number of days to body temperature normalization and number of cough days.However, at this current point of time, no difference was seen in terms of virological cure on day 6 to 7 postinitiation of therapy and composite death or worsening of the disease.Four studies reported efficacy and five studies reported safety of the HCQ + azithromycin combination (out of which three studies from the same group).Although the combination of HCQ + azithromycin seems to be effective and safe, we need more controlled studies to come to an effective conclusion. However, electrocardiographic monitoring is essential while using this combination due to the risk of QT prolongation. [ABSTRACT FROM AUTHOR]

The world has faced the challenges of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for the last two years, first diagnosed at the end of 2019 in Wuhan and widely distributed worldwide. As a result, the WHO has proclaimed the illness brought on by this virus to be a global pandemic. To combat COVID-19, researcher communities continuously develop and implement rapid diagnoses, safe and effective vaccinations and other alternative therapeutic procedures. However, synthetic drug-related side effects and high costs have piqued scientists' interest in natural product-based therapies and medicines. In this regard, antiviral substances derived from natural resources and some medicines have seen a boom in popularity. For instance, algae are a rich source of compounds such as lectins and sulfated polysaccharides, which have potent antiviral and immunity-boosting properties. Moreover, Algae-derived compounds or metabolites can be used as antibodies and vaccine raw materials against COVID-19. Furthermore, some algal species can boost immunity, reduce viral activity in humans and be recommended for usage as a COVID-19 preventative measure. However, this field of study is still in its early stages of development. Therefore, this review addresses critical characteristics of algal metabolites, their antioxidant potential and therapeutic potential in COVID-19. [ABSTRACT FROM AUTHOR]

• Nsp15 is involved in viral replication and suppression of host immune response. • Three bioactive molecules of tea showed high binding affinity with Nsp15. • The molecules selected on basis of robust MD simulations and MMPBSA calculations. • Tea bioactive molecules could be developed as inhibitors of Nsp15 to fight the virus. Immensely aggravated situation of COVID-19 has pushed the scientific community towards developing novel therapeutics to fight the pandemic. Small molecules can possibly prevent the spreading infection by targeting specific vital components of the viral genome. Non-structural protein 15 (Nsp15) has emerged as a promising target for such inhibitor molecules. In this investigation, we docked bioactive molecules of tea onto the active site of Nsp15. Based on their docking scores, top three molecules (Barrigenol, Kaempferol, and Myricetin) were selected and their conformational behavior was analyzed via molecular dynamics simulations and MMPBSA calculations. The results indicated that the protein had well adapted the ligands in the binding pocket thereby forming stable complexes. These molecules displayed low binding energy during MMPBSA calculations, substantiating their strong association with Nsp15. The inhibitory potential of these molecules could further be examined by in-vivo and in-vitro investigations to validate their use as inhibitors against Nsp15 of SARS-CoV2. [ABSTRACT FROM AUTHOR]

Dihydroorotate dehydrogenase (DHODH) is rate-limiting enzyme in biosynthesis of pyrimidone which catalyzes the oxidation of dihydro-orotate to orotate. Orotate is utilized in the biosynthesis of uridine-monophosphate. DHODH inhibitors have shown promise as antiviral agent against Cytomegalovirus, Ebola, Influenza, Epstein Barr and Picornavirus. Anti-SARS-CoV-2 action of DHODH inhibitors are also coming up. In this review, we have reviewed the safety and efficacy of approved DHODH inhibitors (leflunomide and teriflunomide) against COVID-19. In target-centered in silico studies, leflunomide showed favorable binding to active site of MPro and spike: ACE2 interface. In artificial-intelligence/machine-learning based studies, leflunomide was among the top 50 ligands targeting spike: ACE2 interaction. Leflunomide is also found to interact with differentially regulated pathways [identified by KEGG (Kyoto Encyclopedia of Genes and Genomes) and reactome pathway analysis of host transcriptome data] in cogena based drug-repurposing studies. Based on GSEA (gene set enrichment analysis), leflunomide was found to target pathways enriched in COVID-19. In vitro , both leflunomide (EC50 41.49 ± 8.8 μmol/L) and teriflunomide (EC50 26 μmol/L) showed SARS-CoV-2 inhibition. In clinical studies, leflunomide showed significant benefit in terms of decreasing the duration of viral shredding, duration of hospital stay and severity of infection. However, no advantage was seen while combining leflunomide and IFN alpha-2a among patients with prolonged post symptomatic viral shredding. Common adverse effects of leflunomide were hyperlipidemia, leucopenia, neutropenia and liver-function alteration. Leflunomide/teriflunomide may serve as an agent of importance to achieve faster virological clearance in COVID-19, however, findings needs to be validated in bigger sized placebo controlled studies. • Dihydroorotate dehydrogenase (DHODH) inhibitors (leflunomide and its metabolite teriflunomide) have shown potential anti-SARS-CoV-2 action. • In silico drug design studies found leflunomide to bind to active site of MPro and spike: ACE2 interface. Artificial-intelligence/machine-learning based studies identified leflunomide as a potential compound against COVID-19. • In vitro settings, both leflunomide (EC50 41.49 ± 8.8 μmol/L) and teriflunomide (EC50 26 μmol/L) inhibited SARS-CoV-2. • In small sized clinical studies, leflunomide showed significant benefit in decreasing "duration of shredding of SARS-CoV-2", "duration of hospital stay" and "severity of infection". [ABSTRACT FROM AUTHOR]

Bovine rotavirus (BRoV) and bovine coronavirus (BCoV) are major enteric viral pathogens responsible for calve diarrhoea. They are widespread both in dairy and beef cattle throughout the world and causing huge economic losses. The diagnosis of these agents is very difficult due to non-specific nature of lesions and the involvement of some intrinsic and extrinsic risk factors. We performed postmortem of 45 calves, which was below three months of age. Out of 45 necropscid calves, three (6.66%) cases were positive for BRoV and four (8.88%) cases were found positive for BCoV, screened by reverse transcriptase polymerase chain reaction (RT-PCR). Further RT-PCR positive cases were confirmed by immunohistochemistry (IHC) in paraffin-embedded intestinal tissue sections. Three cases of enteritis caused by BRoV showed the hallmark lesions of the shortening and fusion of villi, denudation and infiltration of mononuclear cells in the lamina propria. The BRoV antigen distribution was prominent within the lining epithelium of the villi, peyer's patches in the ileum and strong immunoreactions in the lymphocytes and some macrophages of the mesenteric lymph nodes. Four cases in which BCoV was detected, grossly lesions characterized by colonic mucosa covered with thick, fibrinous and diphtheritic membrane. Histopathologically, jejunum showed skipping lesion of micro-abscesses in crypts. The BCoV antigen distribution was prominent within the necrotic crypts in the jejunum and cryptic micro-abscesses in the colon and ileum. It is the first report of BRoV and BCoV antigen demonstration in the jejunum, colon, ileum, Peyer's patches and mesenteric lymph nodes of naturally infected calves from India by using IHC. • The present study was to investigation of natural cases of BRoV and BCoV infection causing enteritis in dairy calves. • Out of 45 necropscid calves, 6.66% cases for BRoV and 8.88% cases for BCoV were found positive. • BRoV and BCoV antigen demonstration in the jejunum, colon, ileum, Peyer's patches and mesenteric lymph nodes of infected calves by using IHC. [ABSTRACT FROM AUTHOR]