AMFR promotes innate immunity activation and proteasomal degradation of HMGCR in response to influenza virus infection in A549 cells.

Differential regulation of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is considered the rate-limiting enzyme of the cholesterol biosynthesis pathway, has been reported in case of infection with many viruses. In our study, we have found that influenza virus infection decreases total cellular cholesterol level which is directly related to the downregulation of HMGCR protein. We found that HMGCR is degraded through ubiquitination and proteasomal-mediated pathway upon viral infection. Upregulation of Autocrine Motility Factor Receptor (AMFR), which is an E3-ubiquitin ligase of HMGCR, was also observed. Furthermore, knockdown of AMFR inhibits ubiquitination of HMGCR and also leads to inactivation of the innate immunity components TANK-binding kinase 1 (TBK1) and Interferon regulatory factor 3 (IRF3). Our study is the first to show the role of HMGCR and AMFR in influenza virus infection and reveals that AMFR plays a crucial role in the downregulation of HMGCR and the activation of innate immunity following influenza virus infection.

Development of lab score system for predicting COVID-19 patient severity: A retrospective analysis.

AIM: To develop an accurate lab score based on in-hospital patients' potent clinical and biological parameters for predicting COVID-19 patient severity during hospital admission. METHODS: To conduct this retrospective analysis, a derivation cohort was constructed by including all the available biological and clinical parameters of 355 COVID positive patients (recovered = 285, deceased = 70), collected in November 2020-September 2021. For identifying potent biomarkers and clinical parameters to determine hospital admitted patient severity or mortality, the receiver operating characteristics (ROC) curve and Fischer's test analysis was performed. Relative risk regression was estimated to develop laboratory scores for each clinical and routine biological parameter. Lab score was further validated by ROC curve analysis of the validation cohort which was built with 50 COVID positive hospital patients, admitted during October 2021-January 2022. RESULTS: Sensitivity vs. 1-specificity ROC curve (>0.7 Area Under the Curve, 95% CI) and univariate analysis (p<0.0001) of the derivation cohort identified five routine biomarkers (neutrophil, lymphocytes, neutrophil: lymphocytes, WBC count, ferritin) and three clinical parameters (patient age, pre-existing comorbidities, admitted with pneumonia) for the novel lab score development. Depending on the relative risk (p values and 95% CI) these clinical parameters were scored and attributed to both the derivation cohort (n = 355) and the validation cohort (n = 50). ROC curve analysis estimated the Area Under the Curve (AUC) of the derivation and validation cohort which was 0.914 (0.883-0.945, 95% CI) and 0.873 (0.778-0.969, 95% CI) respectively. CONCLUSION: The development of proper lab scores, based on patients' clinical parameters and routine biomarkers, would help physicians to predict patient risk at the time of their hospital admission and may improve hospital-admitted COVID-19 patients' survivability.

Viral Inactivation and Biocompatibility Study of Electrically Activated Water Mist.

In addition to the ongoing global problem of healthcare-acquired infections, the COVID-19 pandemic continues to pose a serious threat to the health of the global population. This unprecedented pandemic situation has reinforced the need for the development of technologies that can curb the transmission of viruses among human beings and help to control the infection. Existing disinfection techniques using either ultraviolet light or harsh chemicals pose safety risks and are not suitable for use in the presence of humans. Thus, the need for a safe and effective disinfection technique that can be used in the presence of humans to control viral transmission is evident. A technique that can continuously disinfect air and surfaces in indoor environments, where the chances of viral transmission are high, can be an indispensable tool to fight such a pandemic. The Airlens Minus Corona (AMC) device provided by Persapien Innovations has been developed to achieve this goal. In this study, the antiviral functionality and biocompatibility of AMC were evaluated. Activated water mist (AWM) generated from this device was tested in vitro and in vivo for its toxicity to cell lines and in animal model. The AWM was found to be non-cytotoxic to L-929 cell lines and had no sign of clinical toxicity in an animal model (rabbit). This device was further used to inactivate animal viruses and bacteriophages. The AWM was found to be effective in the complete inactivation of influenza A H1N1 virus within 5 minutes of direct treatment. This device was also found to be effective in inactivating >90% of bacteriophage particles.

Phage Types of Vibrio cholerae 01 Biotype ElTor Strains Isolated from India during 2012-2017.

BACKGROUND: Cholera is a primordial disease caused by Vibrio cholerae which existed from centuries in different parts of the world and still shows its periodic, endemic and epidemic presence. Thousands of cholera cases are reported from different parts of India and the disease remains endemic throughout the year. At present, we do not have enough knowledge about the phenotypic nature of the circulating V. cholerae strains in this part of the world. OBJECTIVES: This study was carried out over a period of 6 years with the aim defer with the changes in the prevalence and distribution of biotypes, serotypes and phage types of V. cholerae clinical isolates from various endemic regions of the country to determine phenotypic characteristics of the circulating strains and also to predict the attributes of cholera strains responsible for causing significant outbreaks in future. MATERIALS AND METHODS: A total of 1882 V.cholerae O1 isolates from different cholera endemic areas of India were included in this study. V.cholerae strains which were identified as O1 biotype ElTor further analyzed for serotype and phage types using the standard methodologies. Polyvalent O1 and monospecific Inaba and Ogawa antisera were used for serotyping. A panel of five phages of Basu and Mukherjee phage typing scheme and five phages from the new phage typing scheme were used for phage typing analysis following standard methodology. RESULTS: Maximum numbers of strains were isolated from cholera-endemic states like Gujarat and Maharashtra. All the isolates were confirmed as V. cholerae O1 biotype ElTor and majority of them were serotype Ogawa (93.2%). New phage typing scheme resulted in almost 100% typeable V. cholerae O1 strains included in this study and phage type 27 was the predominant type. Although 80% of the strains used in this study were sensitive to all the vibrio phages, S5 phage was found most efficient in lysing cholera strains indicating its broader host range. CONCLUSION: The current study identified phage type 27 as the most dominant type and serotype Ogawa was found continuous in circulation throughout the year which has caused recent cholera outbreaks in India during the past years. Phage sensitivity data propose an alternative cost-effective approach to prevent cholera outbreak by therapeutic uses of typing phages irrespective of origin or clonality of the strains.

Emergence of Novel Coronavirus and COVID-19: whether to stay or die out?

The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus "SARS-CoV-2" (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.