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Zinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with zinc demonstrate better clinical outcomes. The molecular targets and mechanistic details of the anti-coronaviral activity of zinc remain obscure. We show that zinc not only inhibits the SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of the Mpro–Zn2+ complex at 1.9 Å and provide the structural basis of viral replication inhibition. We show that Zn2+ coordinates with the catalytic dyad at the enzyme active site along with two previously unknown water molecules in a tetrahedral geometry to form a stable inhibited Mpro–Zn2+ complex. Further, the natural ionophore quercetin increases the anti-viral potency of Zn2+. As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn2+ mediated inhibition of Mpro may have wider implications. [ABSTRACT FROM AUTHOR]

Chikungunya fever (CHIKF) is an arbovirus disease caused by chikungunya virus (CHIKV), an alphavirus of Togaviridae family. Transmission follows a human-mosquito-human cycle starting with a mosquito bite. Subsequently, symptoms develop after 2–6 days of incubation, including high fever and severe arthralgia. The disease is self-limiting and usually resolve within 2 weeks. However, chronic disease can last up to several years with persistent polyarthralgia. Overlapping symptoms and common vector with dengue and malaria present many challenges for diagnosis and treatment of this disease. CHIKF was reported in India in 1963 for the first time. After a period of quiescence lasting up to 32 years, CHIKV re-emerged in India in 2005. Currently, every part of the country has become endemic for the disease with outbreaks resulting in huge economic and productivity losses. Several mutations have been identified in circulating strains of the virus resulting in better adaptations or increased fitness in the vector(s), effective transmission, and disease severity. CHIKV evolution has been a significant driver of epidemics in India, hence, the need to focus on proper surveillance, and implementation of prevention and control measure in the country. Presently, there are no licensed vaccines or antivirals available; however, India has initiated several efforts in this direction including traditional medicines. In this review, we present the current status of CHIKF in India. [ABSTRACT FROM AUTHOR]

Role of the kidney in outcome of heart failure patients has been a topic of extensive research. Many studies showed that progressive renal dysfunction is often due to decreased blood supply to the kidney which in turn is due to progressive impairment of cardiac function. Most of the studies tried to find out the role of renal dysfunction by estimating serum creatinine and blood urea but none had been succeeded. So clinicians are still in search of a reliable prognostic factor for the heart failure patients. In this longitudinal, self control, interventional study, Ejection Fraction (EF) of 52 patient of AMI was measured by echocardiography before and after angioplasty. Statistical software IBM SPSS trial version 16 was used for analysis of data. We found that as blood urea level increases, improvement in EF decreases. Serum creatinine showed a positive correlation with improvement in EF. It can be hypothesized that patients with higher blood urea showed adverse outcome after PCI while increasing serum creatinine levels showed improvement in EF after percutaneous intervention (PCI) in AMI patients. Increased blood urea level is associated with poor prognosis while an increased serum creatinine level is associated with improved prognosis after PCI in AMI patients. [ABSTRACT FROM AUTHOR]

Introduction: Several Single Nucleotide Polymorphisms (SNPs) in lipid transport genes have been shown to be associated with Coronary Artery Disease (CAD). The Hepatic Lipase (HL) glycoprotein is a key component that catalyzes the hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Aim: We studied whether the HL gene-250G/A polymorphism affect blood lipid level and the CAD in a North Indian population. Materials and Methods: A total number of 477 subjects were enrolled in the study after approval of the Institutional Ethics Committee. Out of 477 subjects, 233 were with coronary artery disease as study group and 244 subjects without coronary artery disease as control group. All subjects recruited with matched ethnicity in age group of 40-70 years. Blood samples were collected in EDTA vials and genomic DNA was extracted from blood using the phenol-chloroform method. Lipid profile was estimated by using a commercially available kit. Polymorphisms in the HL (-250 G/A) gene were analysed by using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP) method. The effect of this polymorphism on plasma lipids, lipoproteins and coronary artery disease was determined. Results: In Human Hepatic Lipase (LIPC)-250G/A genotype, the frequencies of GG, GA and AA genotype in CAD group was 80.69%, 15.45% and 3.86%, respectively; in the control group, the corresponding frequencies were 90.16%, 9.02% and 0.82%, respectively. A significant difference was found in the genotype (LIPC-250G/A) distribution between the two groups. Further logistic regression analysis indicated that the GA and AA genotypes in SNP-250G/A were significantly associated with CAD in all genetic models (In codominant model- GA vs. GG, OR=1.91, 95% CI=1. 09-3.37, p=0. 03 and AA vs. GG, OR= 5.26, 95% CI= 1.10-24.60, p=0.04; in dominant model- GA+AA vs. GG, OR=2.19, p=0.004 and in recessive model- AA vs. GG+GA, OR=5.26, p=0.04 whereas, A allele at nucleotide -250G/A in the LIPC gene had an association with increased risk of CAD (OR=2.33, p=<0.008). Conclusion: Our findings indicated that the higher frequency of a dominant model (GA+AA) as well as mutant allele A of LIPC- 250 G/A polymorphism is significantly associated with risk of CAD and the lipid profile can be used as a predictor of CAD. [ABSTRACT FROM AUTHOR]

Introduction: The change in body position can alter pulmonary functions parameters, therefore it is important to understand the physiological basis of these alteration. Ideally, spirometry is done in sitting position until the subject is unable to do so. Hospitalized patients often assume recumbent body positions irrespective of underlying pathology. Hence, need arises to find out best recumbent body positions for the benefit of these patients to make breathing comfortable for them. Aim: The aim of this study was to find out whether the change from the supine position to crook lying and Fowler's position (45° dorsal elevation) causes change in spirometric parameters. Materials and Methods: The present work was carried out at Department of Physiology, King George's Medical University, Lucknow. A total 131 apparently healthy individuals were enrolled in this cross-sectional study. Lung function was assessed using a PC-based spirometer according to American Thoracic Society guideline in the supine, crook lying and Fowler's position (450 dorsal elevation). results: The study consisted of 131 subjects (male 66%, female 34%), with mean age of 20.15±2.71 years and BMI 21.20±3.28 Kg/ m2. Repeated measures ANOVA with post hoc Bonferroni test was used to compare the mean values between each body position. Compared with the other two positions, Fowler's position showed significantly (p<0.05) higher values for FVC, FEV1, PEF, FEF25-75%. conclusion: Recumbent body position influences spirometric parameters in young healthy subjects. We demonstrated that spirometric values are higher in the Fowler's position than in the supine or crook lying position. The results of this study will help in the selection of the best alternative position for the spirometry in bed ridden patients. [ABSTRACT FROM AUTHOR]

To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus. [ABSTRACT FROM AUTHOR]

Influenza still remains one of the most challenging diseases, posing a significant threat to public health. Host lipid rafts play a critical role in influenza A virus (IAV) assembly and budding, however, their role in polyvalent IAV host binding and endocytosis had remained elusive until now. In the present study, we observed co-localization of IAV with a lipid raft marker ganglioside, GM1, on the host surface. Further, we isolated the lipid raft micro-domains from IAV infected cells and detected IAV protein in the raft fraction. Finally, raft disruption using Methyl-β-Cyclodextrin revealed significant reduction in IAV host binding, suggesting utilization of host rafts for polyvalent binding on the host cell surface. In addition to this, cyclodextrin mediated inhibition of raft-dependent endocytosis showed significantly reduced IAV internalization. Interestingly, exposure of cells to cyclodextrin two hours post-IAV binding showed no such reduction in IAV entry, indicating use of raft-dependent endocytosis for host entry. In summary, this study demonstrates that host lipid rafts are selected by IAV as a host attachment factors for multivalent binding, and IAV utilizes these micro-domains to exploit raft-dependent endocytosis for host internalization, a virus entry route previously unknown for IAV. [ABSTRACT FROM AUTHOR]

Zinc deficiency is linked to poor prognosis in COVID-19 patients while clinical trials with zinc demonstrate better clinical outcomes. The molecular targets and mechanistic details of the anti-coronaviral activity of zinc remain obscure. We show that zinc not only inhibits the SARS-CoV-2 main protease (Mpro) with nanomolar affinity, but also viral replication. We present the first crystal structure of the Mpro-Zn 2+ complex at 1.9 Å and provide the structural basis of viral replication inhibition. We show that Zn 2+ coordinates with the catalytic dyad at the enzyme active site along with two previously unknown water molecules in a tetrahedral geometry to form a stable inhibited Mpro-Zn 2+ complex. Further, the natural ionophore quercetin increases the anti-viral potency of Zn 2+ . As the catalytic dyad is highly conserved across SARS-CoV, MERS-CoV and all variants of SARS-CoV-2, Zn 2+ mediated inhibition of Mpro may have wider implications.

Objectives: Transthoracic electrical bio-impedance (TEB) has been proposed as a non-invasive and continuous method of cardiac output (CO) measurement, but it still has not found wide usages in clinics. The present study measured CO, using a new instrument NICOMON, and compared it with Echocardiography (ECHO) in acute myocardial infarction (AMI) patients., Methods: In the present study 100 patients of AMI were assessed by both ECHO and NICOMON for cardiac output and ECHO is considered as a reference method for comparison. TEB CO was measured by passing an alternating current and measuring the bio-impedance across the thorax. End diastolic volume (EDV), End systolic volume (ESV) & Left ventricular outflow tract (LVOT) diameter, measured by ECHO were used to calculate CO. Various statistical methods like “t”-test & correlation coefficient (r) were used where found suitable., Results: Results: Mean TEB-CO (4.03±1.11 l/min) was significantly higher (p<0.001) than mean ECHO-CO (3.80±1.28 l/min) with a mean difference of 0.25±1.02 l/min., Conclusions: NICOMON measures CO non-invasively but, it needs more elaborative studies on a larger sample to establish it as an alternative method of ECHO for cardiac output measurement on regular basis.