Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies

Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.

COVID-19 Infection in Pregnancy: A Review

Coronavirus disease 2019 (COVID-19), which is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a catastrophic effect on the world's demographics, resulting in more than 3.8 million deaths worldwide, and establishing itself as the most serious global health crisis since the 1918 influenza pandemic. Several questions remain unanswered regarding the effects of COVID-19 disease during pregnancy. Although most infections are mild in high-risk populations, severe disease frequently leads to intubation, intensive care unit admission, and, in some cases, death. Hormonal and physiological changes in the immune and respiratory systems, cardiovascular function, and coagulation may affect the progression of COVID-19 disease in pregnancy. However, consequences of coronavirus infection on implantation, fetal growth and development, labor, and newborn health have yet to be determined, and, consequently, a coordinated global effort is needed in this respect . Principles of management concerning COVID-19 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and co-infection, fetal and uterine contraction monitoring, prevention and / or treatment of thromboembolism early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. This review focuses on COVID-19 during pregnancy, its management, and the area where further investigations are needed to reduce the risk to mothers and their newborns.

The Turn of 20th Contemporary Art under the Big Social Crisis

The current COVID-19 pandemic has immensely impacted artists and their artwork. Such as the spread of the epidemic has led to the emergence of a new art form-NFT and so on, and also made online art exhibitions and virtual spaces became a popular way of viewing exhibitions. The same applies to the 20th century, artists knew that they had entered a unique and modern age of artistic expression. The modern world would bring both opportunities and challenges to the people. Historical evidence has shown that art is a highly dynamic field characterized by its ever-changing nature. Characterized by various social crises such as the Great Depression, 1918 Influenza Pandemic, First World War, and the Second World War, among many others. The Great Depression of the 1930s influenced art, particularly painting, to a great extent. During the depression, art became a tool for reflecting the current conditions, social critique, and activism.

Investigating host-virus interaction mechanism and phylogenetic analysis of viral proteins involved in the pathogenesis

Since the emergence of yellow fever in the Americas and the devastating 1918 influenza pandemic, biologists and clinicians have been drawn to human infecting viruses to understand their mechanisms of infection better and develop effective therapeutics against them. However, the complex molecular and cellular processes that these viruses use to infect and multiply in human cells have been a source of great concern for the scientific community since the discovery of the first human infecting virus. Viral disease outbreaks, such as the recent COVID-19 pandemic caused by a novel coronavirus, have claimed millions of lives and caused significant economic damage worldwide. In this study, we investigated the mechanisms of host-virus interaction and the molecular machinery involved in the pathogenesis of some common human viruses. We also performed a phylogenetic analysis of viral proteins involved in host-virus interaction to understand the changes in the sequence organization of these proteins during evolution for various strains of viruses to gain insights into the viral origin’s evolutionary perspectives.

Racial Disparities in Mortality During the 1918 Influenza Pandemic in United States Cities

The 1918 influenza pandemic stands out because of the unusual age pattern of high mortality. In the United States, another feature merits scientific scrutiny: against a historical backdrop of extreme racial health inequality, the pandemic produced strikingly small ratios of nonwhite to white influenza and pneumonia mortality. We provide the most complete account to date of these racial disparities in 1918, showing that, across U.S. cities, they were almost uniformly small. We examine four potential explanations for this unexpected result, including [1] socio-demographic factors like segregation, [2] city-level implementation of non-pharmaceutical interventions (NPIs), [3] exposure to the milder spring 1918 “herald wave,” and [4] early-life exposures to other influenza strains resulting in differential immunological vulnerability to the 1918 flu. While we find little evidence for 1-3, we offer suggestive evidence that racial variation in early-life exposure to the 1889-1892 influenza pandemic shrunk racial disparities during the 1918 pandemic. We also raise the possibility that differential behavioral responses to the herald wave may have protected nonwhite urban populations. By providing a comprehensive description and careful examination of the potential drivers of racial inequality in mortality during the 1918 pandemic, our study provides a framework to consider interactions between the natural history of particular microbial agents and the social histories of the populations they infect.

Demographic and Evolutionary Consequences of Pandemic Diseases

The ongoing COVID-19 pandemic has justifiably captured the attention of people around the world since late 2019. It has produced in many people a new perspective on or, indeed, a new realization about our potential vulnerability to emerging infectious diseases. However, our species has experienced numerous catastrophic disease pandemics in the past, and in addition to concerns about the harm being produced during the pandemic and the potential long-term sequelae of the disease, what has been frustrating for many public health experts, anthropologists, and historians is awareness that many of the outcomes of COVID-19 are not inevitable and might have been preventable had we actually heeded lessons from the past. We are currently witnessing variation in exposure risk, symptoms, and mortality from COVID-19, but these patterns are not surprising given what we know about past pandemics. We review here the literature on the demographic and evolutionary consequences of the Second Pandemic of Plague (ca. fourteenth–nineteenth centuries C.E.) and the 1918 influenza pandemic, two of the most devastating pandemics in recorded human history. These both provide case studies of the ways in which sociocultural and environmental contexts shape the experiences and outcomes of pandemic disease. Many of the factors at work during these past pandemics continue to be reproduced in modern contexts, and ultimately our hope is that by highlighting the outcomes that are at least theoretically preventable, we can leverage our knowledge about past experiences to prepare for and respond to disease today.

The 1918 Influenza Pandemic: Back to the Future?

<b><i>Background:</i></b> It is just over a century since the 1918 flu pandemic, sometimes referred to as the “mother” of pandemics. This brief retrospective of the 1918 pandemic is taken from the viewpoint of the current SARS-CoV-2/COVID-19 pandemic and is based on a short lecture given during the 2021 Virtual Congress of the ERA-EDTA. <b><i>Summary:</i></b> This review summarizes and highlights some of the earlier pandemic’s salient features, some parallels with today, and some potential learnings, bearing in mind that the flu pandemic occurred over 100 years ago at a time of major turmoil during the climax to WWl, and with limited medical expertise and knowledge, research facilities, or well-structured and resourced healthcare services. While there is little or no information on renal complications at the time, or an effective treatment, some observations in relation to COVID-19 and vaccination are included. <b><i>Key Messages:</i></b> Lessons are difficult to draw from 1918 other than the importance and value of non-pharmaceutical measures to limit viral transmission. While the economic impact of the 1918 pandemic was significant, as it is now with COVID-19, subsequent economic analysis has shown that protecting public health and preserving economic activity are not mutually exclusive. Both H1N1 and SARS-CoV-2 viruses are neurotropic and may cause chronically debilitating neurological diseases, including conditions such as encephalitis lethargica (still debated) and myalgic encephalomyelitis (chronic fatigue syndrome), respectively. Although coronavirus and influenza viral infections have some similarities, they are certainly not the same, as we are realising, and future infectious pandemics may still surprise us, but being “forewarned is forearmed.”

PANDEMONIUM IN PUBLIC HEALTH GOVERNANCE – A SNAPSHOT ON COVID CRISIS

Covid-19 confirmed idiocy of intelligence and perils of powers exasperating the governance ethics of globe and castrated canons of human values. Corona blasted derisively the tenacity and techniques of 'Corona meter' in recording the victimization of health, wealth, economy, environment, education, and governance genuflection before the virility and victory of undaunted virus of SARS genesis. Learned gentry captioned the proliferation of Corona virus as 'Pandemic' of course with doubtful accuracy. The reference of pandemic as a term could have been justified in earlier historical cases of influenza, plague, ebola and SARs etc gracing the meaning of “a set of mutually exacerbating catastrophes” (referring to 1918 Influenza episode) but the present global Corona death dance devastating the material and mental health of individuals, institutions and society needs, probably, a better and appropriate word or phrase. Surprisingly, even before the blink of an eye, health crisis is transformed into multiple conundrums – economic, research, medical, political and governance mocking at all public and private institutions.

COVID-19 and Cancer Therapy: Interrelationships and Management of Cancer Cases in the Era of COVID-19

The COVID-19 global epidemic poses this generation’s biggest worldwide public health challenge probably since the 1918 influenza epidemic. Recent reports on two new variants have triggered a dramatic upsurge in research to understand the pandemic, primarily focussing on the virology, triggers, clinical characteristics, and diagnostic tests including the prevention and management of the novel coronavirus. Whilst such studies are important in managing the present medical emergency, there is a need for further work to include interdependencies between the epidemic and other illnesses. This will help in developing effective approaches to treat and manage associated diseases in both the short and the long term. In this regard, people living with cancer are a subgroup that is highly vulnerable to respiratory infections and acute pneumonitis similar to the one caused by the COVID-19 virus. This is because the state of their immunity is compromised due to malignancy and the adverse effects of anticancer treatments. With annual cancer projections rising globally and an estimated 70 percent of all cancer-related deaths occurring in low- and middle-income countries, the patient population with impaired immune systems that could be adversely impacted by COVID-19 is only anticipated to rise. In this review, we delve into the challenges and health risks facing cancer patients and cancer treatment in the COVID-19 context, with suggestions into viable measures which can be taken to minimize exposure to the risk of contracting COVID-19 for this vulnerable subgroup. New mutations and the prospects offered by vaccines development and how they relate to this class of patients are also discussed.