The heat stability of hepatitis B virus

During the World War II jaundice and hepatitis in the US army were observed after vaccination with the yellow fever vaccine containing human plasma for stabilization. This led to first heat experiments with volunteers without knowledge of the causative agents. Finally, experiments of human serum with volunteers and chimpanzees led to the conclusion that the hepatitis B virus (HBV) which had been identified as the responsible agent of the contamination of the vaccine, could not be inactivated at 98°C after 1 min, whereas 2 min in two chimpanzees were enough. Meanwhile, a cell culture system became available showing that 2 min exposure time is not enough depending on the virus strain used whereas 5 min means complete inactivation of HBV. The great stability of the blood-borne HBV was also of interest in hospital hygiene due to the use of moist heat for disinfection of heat-stable medical devices in washer-disinfectants. The requirements for washer-disinfectors and the parameters describing disinfection with moist heat are defined in the EN ISO 15883. In this standard, the efficacy of this thermal disinfection is described by the A$_0$ value. For heat-resistant viruses a higher A$_0$ = 3,000 is often recommended including semi-critical instruments that undergo thermal disinfection and no final sterilization. All experiments including volunteers, chimpanzees and now cell culture were performed with greater A$_0$ values than 3,000. Therefore, an A$_0$ value of 3,000 e.g., being reached by 90°C and 5 min in washer-disinfectants, can easily elevated to 6,000 by prolongation of the exposure time to 10 min. In contrast to the different laboratory experiments with high virus titers it should be considered that in practice the necessary cleaning step upfront will help to reduce virus load and then protect the personnel in the medical area

In vitro lung models and their application to study SARS-CoV-2 pathogenesis and disease

SARS-CoV-2 has spread across the globe with an astonishing velocity and lethality that has put scientist and pharmaceutical companies worldwide on the spot to develop novel treatment options and reliable vaccination for billions of people. To combat its associated disease COVID-19 and potentially newly emerging coronaviruses, numerous pre-clinical cell culture techniques have progressively been used, which allow the study of SARS-CoV-2 pathogenesis, basic replication mechanisms, and drug efficiency in the most authentic context. Hence, this review was designed to summarize and discuss currently used in vitro and ex vivo cell culture systems and will illustrate how these systems will help us to face the challenges imposed by the current SARS-CoV-2 pandemic

Persistence of pathogens on inanimate surfaces

For the prevention of infectious diseases, knowledge about transmission routes is essential. In addition to respiratory, fecal–oral, and sexual transmission, the transfer of pathogens via surfaces plays a vital role for human pathogenic infections - especially nosocomial pathogens. Therefore, information about the survival of pathogens on surfaces can have direct implications on clinical measures, including hygiene guidelines and disinfection strategies. In this review, we reviewed the existing literature regarding viral, bacterial, and fungal persistence on inanimate surfaces. In particular, the current knowledge of the survival time and conditions of clinically relevant pathogens is summarized. While many pathogens persist only for hours, common nosocomial pathogens can survive for days to weeks under laboratory conditions and thereby potentially form a continuous source of transmission if no adequate inactivation procedures are performe

Beyond the usual suspects

Hepatitis E virus infections are the leading cause of viral hepatitis in humans, contributing to an estimated 3.3 million symptomatic cases and almost 44,000 deaths annually. Recently, HEV infections have been found to result in chronic liver infection and cirrhosis in severely immunocompromised patients, suggesting the possibility of HEV-induced hepatocarcinogenesis. While HEV-associated formation of HCC has rarely been reported, the expansion of HEV's clinical spectrum and the increasing evidence of chronic HEV infections raise questions about the connection between HEV and HCC. The present review summarizes current clinical evidence of the relationship between HEV and HCC and discusses mechanisms of virus-induced HCC development with regard to HEV pathogenesis. We further elucidate why the development of HEV-induced hepatocellular carcinoma has so rarely been observed and provide an outlook on possible experimental set-ups to study the relationship between HEV and HCC formation

Stability of pathogens on banknotes and coins

For the prevention of infectious diseases, knowledge about potential transmission routes is essential. Pathogens can be transmitted directly (i.e. respiratory droplets, hand-to-hand contact) or indirectly via contaminated surfaces (fomites). In particular, frequently touched objects/surfaces may serve as transmission vehicles for different clinically relevant bacterial, fungal, and viral pathogens. Banknotes and coins offer ample surface area and are frequently exchanged between individuals. Consequently, many concerns have been raised in the recent past, that banknotes and coins could serve as vectors for the transmission of disease-causing microorganisms. This review summarizes the latest research on the potential of paper currency and coins to serve as sources of pathogenic viral, bacterial, and fungal agents. In contrast to the current perception of banknotes and coins as important transmission vehicles, current evidence suggests, that banknotes and coins do not pose a particular risk of pathogen infection for the public

Anti-infective properties of the golden spice curcumin

The search for novel anti-infectives is one of the most important challenges in natural product research, as diseases caused by bacteria, viruses, and fungi are influencing the human society all over the world. Natural compounds are a continuing source of novel anti-infectives. Accordingly, curcumin, has been used for centuries in Asian traditional medicine to treat various disorders. Numerous studies have shown that curcumin possesses a wide spectrum of biological and pharmacological properties, acting, for example, as anti-inflammatory, anti-angiogenic and anti-neoplastic, while no toxicity is associated with the compound. Recently, curcumin’s antiviral and antibacterial activity was investigated, and it was shown to act against various important human pathogens like the influenza virus, hepatitis C virus, HIV and strains of $\it Staphylococcus$, $\it Streptococcus$, and $\it Pseudomonas$. Despite the potency, curcumin has not yet been approved as a therapeutic antiviral agent. This review summarizes the current knowledge and future perspectives of the antiviral, antibacterial, and antifungal effects of curcumin

Nanoscale copper and silver thin film systems display differences in antiviral and antibacterial properties

The current Coronavirus Disease 19 (COVID-19) pandemic has exemplified the need for simple and efficient prevention strategies that can be rapidly implemented to mitigate infection risks. Various surfaces have a long history of antimicrobial properties and are well described for the prevention of bacterial infections. However, their effect on many viruses has not been studied in depth. In the context of COVID-19, several surfaces, including copper (Cu) and silver (Ag) coatings have been described as efficient antiviral measures that can easily be implemented to slow viral transmission. In this study, we detected antiviral properties against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) on surfaces, which were coated with Cu by magnetron sputtering as thin Cu films or as Cu/Ag ultrathin bimetallic nanopatches. However, no effect of Ag on viral titers was observed, in clear contrast to its well-known antibacterial properties. Further enhancement of Ag ion release kinetics based on an electrochemical sacrificial anode mechanism did not increase antiviral activity. These results clearly demonstrate that Cu and Ag thin film systems display significant differences in antiviral and antibacterial properties which need to be considered upon implementation

Hepatitis E virus drug development

Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-$\alpha$ (pegIFN-$\alpha$). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-$\alpha$, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV

Characterization of equine parvovirus in thoroughbred breeding horses from Germany

An equine parvovirus-hepatitis (EqPV-H) has been recently identified in association with equine serum hepatitis, also known as Theiler's disease. The disease was first described by Arnold Theiler in 1918 and is often observed with parenteral use of blood products in equines. However, natural ways of viral circulation and potential risk factors for transmission still remain unknown. In this study, we investigated the occurrence of EqPV-H infections in Thoroughbred horses in northern and western Germany and aimed to identify potential risk factors associated with viral infections. A total of 392 Thoroughbreds broodmares and stallions were evaluated cross-sectionally for the presence of anti-EqPV-H antibodies and EqPV-H DNA using a luciferase immunoprecipitation assay (LIPS) and a quantitative PCR, respectively. In addition, data regarding age, stud farm, breeding history, and international transportation history of each horse were collected and analysed. An occurrence of 7% EqPV-H DNA positive and 35% seropositive horses was observed in this study cohort. The systematic analysis of risk factors revealed that age, especially in the group of 11–15-year-old horses, and breeding history were potential risk factors that can influence the rate of EqPV-H infections. Subsequent phylogenetic analysis showed a high similarity on nucleotide level within the sequenced Thoroughbred samples. In conclusion, this study demonstrates circulating EqPV-H infections in Thoroughbred horses from central Europe and revealed age and breeding history as risk factors for EqPV-H infections

Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance

Even 30 years after the discovery of the hepatitis C virus (HCV) in humans there is still no vaccine available. Reasons for this include the high mutation rate of HCV, which allows the virus to escape immune recognition and the absence of an immunocompetent animal model for vaccine development. Phylogenetically distinct hepaciviruses (genus $\it Hepacivirus$, family $\it Flaviviridae$) have been isolated from diverse species, each with a narrow host range: the equine hepacivirus (EqHV) is the closest known relative of HCV. In this study, we used amplicon-based deep-sequencing to investigate the viral intra-host population composition of the genomic regions encoding the surface glycoproteins E1 and E2. Patterns of E1E2 substitutional evolution were compared in longitudinally sampled EqHV-positive sera of naturally and experimentally infected horses and HCV-positive patients. Intra-host virus diversity was higher in chronically than in acutely infected horses, a pattern which was similar in the HCV-infected patients. However, overall glycoprotein variability was higher in HCV compared to EqHV. Additionally, selection pressure in HCV populations was higher, especially within the N-terminal region of E2, corresponding to the hypervariable region 1 (HVR1) in HCV. An alignment of glycoprotein sequences from diverse hepaciviruses identified the HVR1 as a unique characteristic of HCV: hepaciviruses from non-human species lack this region. Together, these data indicate that EqHV infection of horses could represent a powerful surrogate animal model to gain insights into hepaciviral evolution and HCVs HVR1-mediated immune evasion strategy