Temperature dependent viral tropism: understanding viral seasonality and pathogenicity as applied to the avoidance and treatment of endemic viral respiratory illnesses.

This review seeks to explain three features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness and the rapid response of outbreaks to weather, specifically temperature; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called temperature dependent viral tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can spread more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This can confine them to the upper respiratory tract and allow them to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that 'wild' respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the occurrence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. TDVT has important practical implications for preventing and treating respiratory illness including Covid-19. It is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

Metallic Structures: Effective Agents to Fight Pathogenic Microorganisms.

The current worldwide pandemic caused by coronavirus disease 2019 (COVID-19) had alerted the population to the risk that small microorganisms can create for humankind's wellbeing and survival. All of us have been affected, directly or indirectly, by this situation, and scientists all over the world have been trying to find solutions to fight this virus by killing it or by stop/decrease its spread rate. Numerous kinds of microorganisms have been occasionally created panic in world history, and several solutions have been proposed to stop their spread. Among the most studied antimicrobial solutions, are metals (of different kinds and applied in different formats). In this regard, this review aims to present a recent and comprehensive demonstration of the state-of-the-art in the use of metals, as well as their mechanisms, to fight different pathogens, such as viruses, bacteria, and fungi.

Antivirals that target the host IMPα/ß1-virus interface.

Although transport into the nucleus mediated by the importin (IMP) α/ß1-heterodimer is central to viral infection, small molecule inhibitors of IMPα/ß1-dependent nuclear import have only been described and shown to have antiviral activity in the last decade. Their robust antiviral activity is due to the strong reliance of many different viruses, including RNA viruses such as human immunodeficiency virus-1 (HIV-1), dengue (DENV), and Zika (ZIKV), on the IMPα/ß1-virus interface. High-throughput compound screens have identified many agents that specifically target this interface. Of these, agents targeting IMPα/ß1 directly include the FDA-approved macrocyclic lactone ivermectin, which has documented broad-spectrum activity against a whole range of viruses, including HIV-1, DENV1-4, ZIKV, West Nile virus (WNV), Venezuelan equine encephalitis virus, chikungunya, and most recently, SARS-CoV-2 (COVID-19). Ivermectin has thus far been tested in Phase III human clinical trials for DENV, while there are currently close to 80 trials in progress worldwide for SARS-CoV-2; preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit. Agents that target the viral component of the IMPα/ß1-virus interface include N-(4-hydroxyphenyl) retinamide (4-HPR), which specifically targets DENV/ZIKV/WNV non-structural protein 5 (NS5). 4-HPR has been shown to be a potent inhibitor of infection by DENV1-4, including in an antibody-dependent enhanced animal challenge model, as well as ZIKV, with Phase II clinical challenge trials planned. The results from rigorous RCTs will help determine the therapeutic potential of the IMPα/ß1-virus interface as a target for antiviral development.

Emerging/re-emerging viral diseases & new viruses on the Indian horizon.

Infectious diseases remain as the major causes of human and animal morbidity and mortality leading to significant healthcare expenditure in India. The country has experienced the outbreaks and epidemics of many infectious diseases. However, enormous successes have been obtained against the control of major epidemic diseases, such as malaria, plague, leprosy and cholera, in the past. The country's vast terrains of extreme geo-climatic differences and uneven population distribution present unique patterns of distribution of viral diseases. Dynamic interplays of biological, socio-cultural and ecological factors, together with novel aspects of human-animal interphase, pose additional challenges with respect to the emergence of infectious diseases. The important challenges faced in the control and prevention of emerging and re-emerging infectious diseases range from understanding the impact of factors that are necessary for the emergence, to development of strengthened surveillance systems that can mitigate human suffering and death. In this article, the major emerging and re-emerging viral infections of public health importance have been reviewed that have already been included in the Integrated Disease Surveillance Programme.

Prioritization of High Consequence Viruses to Improve European Laboratory Preparedness for Cross-Border Health Threats.

Highly infectious diseases can spread rapidly across borders through travel or trade, and international coordination is essential to a prompt and efficient response by public health laboratories. Therefore, developing strategies to identify priorities for a rational allocation of resources for research and surveillance has been the focus of a large body of research in recent years. This paper describes the activities and the strategy used by a European-wide consortium funded by the European Commission, named EMERGE (Efficient response to highly dangerous and emerging pathogens at EU level), for the selection of high-threat pathogens with cross-border potential that will become the focus of its preparedness activities. The approach used is based on an objective scoring system, a close collaboration with other networks dealing with highly infection diseases, and a diagnostic gaps analysis. The result is a tool that is simple, objective and adaptable, which will be used periodically to re-evaluate activities and priorities, representing a step forward towards a better response to infectious disease emergencies.

U.S. kills effort to hunt dangerous viruses.

Critics feared DEEP VZN project could help pathogens jump from animals to humans.

Molecular tweezers - a new class of potent broad-spectrum antivirals against enveloped viruses.

A new supramolecular approach to broad spectrum antivirals utilizes host guest chemistry between molecular tweezers and lysine/arginine as well as choline. Basic amino acids in amyloid-forming SEVI peptides (semen-derived enhancers of viral infection) are included inside the tweezer cavity leading to disaggregation and neutralization of the fibrils, which lose their ability to enhance HIV-1/HIV-2 infection. Lipid head groups contain the trimethylammonium cation of choline; this is likewise bound by molecular tweezers, which dock onto viral membranes and thus greatly enhance their surface tension. Disruption of the envelope in turn leads to total loss of infectiosity (ZIKA, Ebola, Influenza). This complexation event also seems to be the structural basis for an effective inihibition of cell-to-cell spread in Herpes viruses. The article describes the discovery of novel molecular recognition motifs and the development of powerful antiviral agents based on these host guest systems. It explains the general underlying mechanisms of antiviral action and points to future optimization and application as therapeutic agents.

Special Issue "Emerging Virus Infections in Adverse Pregnancy Outcomes".

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Polysaccharides and Their Derivatives as Potential Antiviral Molecules.

In the current context of the COVID-19 pandemic, it appears that our scientific resources and the medical community are not sufficiently developed to combat rapid viral spread all over the world. A number of viruses causing epidemics have already disseminated across the world in the last few years, such as the dengue or chinkungunya virus, the Ebola virus, and other coronavirus families such as Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). The outbreaks of these infectious diseases have demonstrated the difficulty of treating an epidemic before the creation of vaccine. Different antiviral drugs already exist. However, several of them cause side effects or have lost their efficiency because of virus mutations. It is essential to develop new antiviral strategies, but ones that rely on more natural compounds to decrease the secondary effects. Polysaccharides, which have come to be known in recent years for their medicinal properties, including antiviral activities, are an excellent alternative. They are essential for the metabolism of plants, microorganisms, and animals, and are directly extractible. Polysaccharides have attracted more and more attention due to their therapeutic properties, low toxicity, and availability, and seem to be attractive candidates as antiviral drugs of tomorrow.

[Pilgrims to Mecca, germs and the international community]. / Les pèlerins de La Mecque, les germes et la communauté internationale.

With steam navigation, men, but also seeds of diseases, move faster. In 1865, the pilgrimage to Mecca induced a terrible cholera pandemic. This caused deep trauma in Europe and prompted the international community, recently born, to focus on the pilgrims who were regarded as the main "risk group" in the spread of epidemics. Through a series of international sanitary conferences, European powers, in agreement with the Ottoman Empire, imposed a heavy control over the pilgrims, much harsher than that applied to ordinary commercial navigation exchanges. These decisions led to the establishment of a huge quarantine device in the Red Sea and the Levant, including two lazaretto, one at the entrance and the other at the exit of the Red Sea, where the pilgrims were trapped and disinfected during their sacred journey. This contrasted with the concommitant disappearance of quarantines everywhere else. The pilgrims did not show hostility towards medical and prophylactic treatments but protested against the dehumanizing conditions of their realization. The combined pressures of nationalism and sovereignty claims from Saudi Arabia ended this system in 1957.

Emerging Hepatotropic Viruses in Cats: A Brief Review.

The possible role of viruses in feline liver disease has long remained neglected. However, in 2018, an analogue of human hepatitis B virus was identified in cats. Moreover, antibodies for human hepatitis E have been detected consistently at various prevalence rates in cats. Although the correlation between these viruses and the liver injury in cats must be clarified, hepatotropic viruses might represent an increasing risk for feline and public health.

Viral Infections of the Upper Airway in the Setting of COVID-19: A Primer for Rhinologists.

BACKGROUND: Viral respiratory tract infections are associated with a significant burden of disease and represent one of the leading causes of mortality worldwide. The current Coronavirus Disease 2019 (COVID-19) pandemic highlights the devastating toll that respiratory viruses have on humanity and the desperate need to understand the biological characteristics that define them in order to develop efficacious treatments and vaccines. To date, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected nearly 600 times more people and resulted in 200 times more deaths relative to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) combined. OBJECTIVE: Through this review, we aim to summarize the key characteristics of respiratory viruses that hold global significance, with a focus on SARS-CoV-2. Our goal is to disseminate our current knowledge of these infectious agents to otolaryngologists, in particular rhinologists, practicing in the COVID-19 era. METHODS: The general and clinical characteristics of selected respiratory viruses along with available viral treatments and vaccines are reviewed. RESULTS: There has been significant progress in our understanding of the epidemiology and pathogenesis of various respiratory viruses. However, despite the advancement in knowledge, efficacious vaccines and antiviral treatments remain elusive for most respiratory viruses. The dire need for these scientific discoveries is highlighted by the recent COVID-19 pandemic, which has prompted investigators worldwide to conduct clinical trials at an accelerated timeline in an effort to reduce the morbidity and mortality associated with SARS-CoV-2 infection. Rhinologists will continue to remain on the front-lines of pandemics associated with respiratory viruses. CONCLUSION: In light of these unprecedented times, the need to understand the nuances of these viral respiratory pathogens, especially SARS-CoV-2, cannot be overemphasized. This knowledge base is of particular importance to otolaryngologists, whose expertise in the upper airway coincides with the anatomic tropism of these infectious agents.

New tools for the study and direct surveillance of viral pathogens in water.

Half a century ago scientists attempted the detection of poliovirus in water. Since then other enteric viruses responsible for gastroenteritis and hepatitis have replaced enteroviruses as the main target for detection. However, most viral outbreaks are restricted to norovirus and hepatitis A virus, making them the main targets in water. The inclusion of virus analysis in regulatory standards for viruses in water samples must overcome several shortcomings such as the technical difficulties and high costs of virus monitoring, the lack of harmonised and standardised assays and the challenge posed by the ever-changing nature of viruses. However, new tools are nowadays available for the study and direct surveillance of viral pathogens in water that may contribute to fulfil these requirements.

Consequences of Pathogen Lists: Why Some Diseases May Continue to Plague Us.

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to specific goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that address what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.

VII International Symposium on Respiratory Viral Infections.

The VII International Symposium on Respiratory Viral Infections was a multidisciplinary forum for the presentation of recent advances in respiratory virus research with special emphasis on antiviral therapies and vaccine strategies. Topics covered in invited lectures included detection of novel respiratory viral pathogens and viral evolution, characterization of the 1918 pandemic virus, human metapneumovirus infections, human respiratory epithelial cultures for studying viral pathogenesis, the role of respiratory viruses in the pathogenesis of asthma, influenza-bacterial interactions, advances in generating vaccine candidates against global respiratory threats like avian influenza and SARS, antiviral resistance surveillance in influenza viruses, and a mini-symposium on advances in viral diagnostics. Other talks covered the live, attenuated intranasal influenza vaccine, monoclonals for respiratory syncytial virus (RSV), mechanisms of antiviral resistance in influenza B, and novel inhibitors for influenza, RSV and rhinovirus infections.

Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.

Processes for managing pathogens.

Wastewater contains human, animal, and plant pathogens capable of causing viral, bacterial, or parasitic infections. There are several routes whereby sewage pathogens may affect human health, including direct contact, contamination of food crops, zoonoses, and vectors. The range and numbers of pathogens in municipal wastewater vary with the level of endemic disease in the community, discharges from commercial activities, and seasonal factors. Regulations to control pathogen risk in the United States and Europe arising from land application of biosolids are based on the concept of multiple barriers to the prevention of transmission. The barriers are (i) treatment to reduce pathogen content and vector attraction, (ii) restrictions on crops grown on land to which biosolids have been applied, and (iii) minimum intervals following application and grazing or harvesting. Wastewater treatment reduces number of pathogens in the wastewater by concentrating them with the solids in the sludge. Although some treatment processes are designed specifically to inactivate pathogens, many are not, and the actual mechanisms of microbial inactivation are not fully understood for all processes. Vector attraction is reduced by stabilization (reduction of readily biodegradable material) and/or incorporation immediately following application. Concerns about health risks have renewed interest in the effects of treatment (on pathogens) and advanced treatment methods, and work performed in the United States suggests that Class A pathogen reduction can be achieved less expensively than previously thought. Effective pathogen risk management requires control to the complete chain of sludge treatment, biosolids handling and application, and post-application activities. This may be achieved by adherence to quality management systems based on hazard analysis critical control point (HACCP) principles.