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Background: Regulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT)., Methods: Three groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t -test or Wilcoxon rank test was applied for pre-post comparison and the Student's t -test or Mann-Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points., Results: A significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention ( p < 0.001) and control groups ( p = 0.003), indicating no role of intervention on change in WBC number. WBC count ( p = 0.002) and D-dimer ( p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls ( p = 0.01). D-dimer was the primary outcome, which remained below 0.50 μg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients ( p = 0.01) and HCWs ( p = 0.002) after intervention. The high-frequency power ( p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed., Conclusion: Yogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID., Trial Registration: http://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rain, Puri, Bhalla, Avti, Subramaniam, Kaushal, Srivastava, Mahajan, Singh, Pandey, Malhotra, Goel, Kumar, Sachdeva, Maity, Verma, Dixit, Gupta, Mehra, Nadholta, Khosla, Ahuja and Anand.)

The coronavirus disease 2019 (COVID-19) pandemic is caused by newly discovered severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). One of the striking targets amongst all the proteins in coronavirus is the main protease (M pro ), as it plays vital biological roles in replication and maturation of the virus, and hence the potential target. The aim of this study is to repurpose the Food and Drug Administration (FDA) approved molecules via computer-aided drug designing against M pro (PDB ID: 6Y2F) of SARS CoV-2 due to its high x-ray resolution of 1.95   Å as compared to other published M pro structures. High Through Virtual Screening (HTVS) of 2456 FDA approved drugs using structure-based docking were analyzed. Molecular Dynamics simulations were performed to check the overall structural stability (RMSD), Cα fluctuations (RMSF) and protein-ligand interactions. Further, trajectory analysis was performed to assess the binding quality by exploiting the protein-residue motion cross correlation (DCCM) and binding free energy (MM/GBSA). Tenofovir, an antiretroviral for HIV-proteases and Terlipressin, a vasoconstrictor show stable RMSD, RMSF, better MM/GBSA with good cross correlation as compared to the Apo and O6K. Moreover, the results show concurrence with Nelfinavir, Lopinavir and Ritonavir which have shown significant inhibition in in vitro studies. Therefore, we conclude that Tenofovir and Terlipresssin might also show protease inhibition but are still open to clinical validation in case of SARS-CoV 2 treatment.Communicated by Ramaswamy H. Sarma.

The advent of SARS-CoV-2 has become a universal health issue with no appropriate cure available to date. The coronavirus nucleocapsid (N) protein combines viral genomic RNA into a ribonucleoprotein and protects the viral genome from the host's nucleases. Structurally, the N protein comprises two independent domains: the N-terminal domain (NTD) for RNA-binding and C-terminal domain (CTD) involved in RNA-binding, protein dimerization, and nucleocapsid stabilization. The present study explains the structural aspects associated with the involvement of nucleocapsid C-terminal domain in the subunit assembly that helps the RNA binding and further stabilizing the virus assembly by protecting RNA from the hosts exonucleases degradation. The molecular dynamics (MD) simulations of the N-CTD and RNA complex suggests two active sites (site I: a monomer) and (site II: a dimer) with structural stability (RMSD: ~2 Å), Cα fluctuations (RMSF: ~3 Å) and strong protein-ligand interactions were estimated through the SiteMap module of Schrodinger. Virtual screening of 2456 FDA-approved drugs using structure-based docking identified top two leads distinctively against Site-I (monomer): Ceftaroline fosamil (MM-GBSA = -47.12 kcal/mol) and Cefoperazone (-45.84 kcal/mol); and against Site-II (dimer): Boceprevir, (an antiviral protease inhibitor, -106.78 kcal/mol) and Ceftaroline fosamil (-99.55 kcal/mol). The DCCM and PCA of drugs Ceftaroline fosamil (PC1+PC2 = 71.9%) and Boceprevir (PC1 +PC2 = 61.6%) show significant correlated residue motions which suggests highly induced conformational changes in the N-CTD dimer. Therefore, we propose N-CTD as a druggable target with two active binding sites (monomer and dimer) involved in specific RNA binding and stability. The RNA binding site with Ceftaroline fosamil binding can prevent viral assembly and can act as an antiviral for coronavirus., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment., Competing Interests: None

Knowledge of a new mutant strain of SARS-coronavirus (CoV-2) is enormously essential to identify a targeted drug and for the development of the vaccine. In this article, we systematically reviewed the different mutation strains (variant of concern [VOC] and variant of interest [VOI]) which were found in different countries such as the UK, Singapore, China, Germany, Vietnam, Western Africa, Dublin, Ireland, Brazil, Iran, Italy, France, America, and Philippines. We searched four literature databases (PubMed, EMBASE, NATURE, and Willey online library) with suitable keywords and the time filter was November 2019 to June 16, 2021. To understand the worldwide spread of variants of SARS-CoV-2, we included a total of 27 articles of case reports, clinical and observational studies in the systematic review. However, these variants mostly spread because of their ability to increase transmission, virulence, and escape immunity. So, in this paper is we found mutated strains of SARS-CoV-2 like VOCs that are found in different regions across the globe are ALPHA strain in the U.K, BETA strain in South Africa, GAMMA strain in Brazil, Gamma and Beta strains in European Countries, and some VOIs like Theta variant in the Philippines., Competing Interests: None

The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on 'docking score'. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class 'bronchodilators' and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma.

BackgroundRegulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT).MethodsThree groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann–Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points.ResultsA significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 μg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed.ConclusionYogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID.Trial registrationhttp://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.

• Cell lines are best In-Vitro experimental models for standardization and validation of novel and repurposing of drugs. • SARS-CoV-2 entrance is very specific to target cells through ACE2, CD147 and TMPRSS2 receptors. • Our systematic review addresses the utility of SARS COV-2 specific cell lines as potential In-Vitro models. • Elucidated all In-Vitro studies done for SARS-CoV-2 isolation, pathogenesis, and therapeutics. • VeroE6, HEK293, Huh-7 and Caco2 have high ACE2 and TMPRSS2 expression and are potential In-Vitro models for SARS-CoV-2. In-Vitro /Cellular evidence is the backbone and vital proof of concept during the development of novel therapeutics as well as drugs repurposing against COVID-19. Choosing an ideal in-vitro model is vital as the virus entry is through ACE2, CD147, and TMPRSS2 dependant and very specific. In this regard, this is the first systematic review addressing the importance of specific cell lines used as potential in-vitro models in the isolation, pathogenesis, and therapeutics for SARS−COV-2. We searched 17 literature databases with appropriate keywords, and identified 1173 non-duplicate studies. In the present study, 71 articles are included after a careful, thorough screening of the titles and their abstracts for possible inclusion using predefined inclusion/exclusion criteria (PRISMA Guidelines). In the current study, we compiled cell culture-based studies for SARS-CoV-2 and found the best compatible In-Vitro models for SARS-CoV-2 (Vero, VeroE6, HEK293 as well as its variants, Huh-7, Calu-3 2B4, and Caco2). Among other essential cell lines used include LLC-MK2, MDCKII, BHK-21, HepG2, A549,T cell leukemia (MT-2), stems cells based cell line DYR0100for differentiation assays, and embryo-specific NIH3T3 cell line for vaccine production. The Present study provides a detailed summary of all the drugs/compounds screened for drug repurposing and discovery purpose using the in-vitro models for SARS-CoV-2 along with isolation, pathogenesis and vaccine production. This study also suggests that after careful evaluation of all the cell line based studies, Kidney cells (VeroE6, HEK293 along with their clones), liver Huh-7cells, respiratory Calu-3 cells, and intestinal Caco-2 are the most widely used in-vitro models for SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The global impact of Coronavirus Disease 2019 (COVID-19) is tremendous on human life, not only affecting the physical and mental health of population but also impacting the economic system of countries and individual itself. The present situation demands prompt response toward COVID-19 by equipping the humans with strategies to overcome the infection and stress associated with it. These strategies must not only be limited to preventive and therapeutic measures, but also aim at improving immunity and mental health. This can be achieved by yogic breathing techniques. In this perspective, we emphasize the importance of yogic breathing, Simha Kriya and Isha kriya, the simple yet effective breathing techniques.