Hantavirus Pulmonary Syndrome Research Articles

Incidence of Orthohantavirus infection in humans follows observed changes in rodent reservoirs, Hubei Province, China (1984-2010).

Orthohantaviruses (genus Orthohantavirus, family Hantaviridae of order Bunyavirales) are rodent-borne viruses causing 2 human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), which are mainly prevalent in Eurasia and the Americas, respectively. We initiated this study to investigate and analyze the Orthohantaviruses infection in rodent reservoirs and humans in the Hubei Province of China from 1984 to 2010. The study included 10,314 mouse and 43,753 human serum samples. In this study, we analyzed the incidence of Orthohantavirus infection in humans and observed changes in rodent reservoirs in Hubei Province. The results indicated that although the incidence of HFRS declined from the 1990s, the human inapparent infection did not decrease dramatically. Although elements of the disease ecology have changed over the study period, Apodemus agrarius and Rattus norvegicus remain the major species and a constituent ratio of Rattus norvegicus increased. Rodent population density fluctuated between 16.65% and 2.14%, and decreased quinquennially, showing an obvious downward trend in recent years. The average orthohantaviruses-carrying rate was 6.36%, of which the lowest rate was 2.92% from 2006 to 2010. The analysis of rodent species composition showed that Rattus norvegicus and Apodemus agrarius were the dominant species over time (68.6% [1984 to 1987] and 90.4% [2000 to 2011]), while the composition and variety of other species decreased. The density of rodents was closely related to the incidence of HFRS (r = 0.910, P = .032). Our long-term investigation demonstrated that the occurrence of HFRS is closely related to rodent demographic patterns. Therefore, rodent monitoring and rodent control measures for prevention against HFRS in Hubei are warranted.

Hantavirus Diseases – A Comprehensive Review

Hantaviruses are a diverse group of infectious agents which are zoonotic in nature and transmitted to humans through rodent reservoir. Hantaviruses are enveloped RNA viruses that persistently infect rodent hosts without ill-effect. The host persistently excretes virus in urine and saliva. Man becomes infected from the rodents when one enters the ecological niche of the other. Hantaviruses can cause two types of diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and Hantavirus cardiopulmonary syndrome (HCPS). The number of reported Hantavirus infections is increasing worldwide, and new Hantaviruses are being discovered in many countries, making them a global public health concern. Hantavirus infections are thought to be under diagnosed due to the fact that they frequently cause asymptomatic and nonspecific mild infections, as well as a lack of simple standardized diagnostic laboratory methods. This review summarizes current knowledge on Hantaviral infections, including virology, epidemiology, clinical manifestations, laboratory diagnostics, treatment, and prevention.

Design and validation of a novel multi-epitopes vaccine against hantavirus

Hantavirus is a member of the order Bunyavirales and an emerging global pathogen. Hantavirus infections have affected millions of people globally based on available epidemiological data and research studies. Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are the two main human diseases associated with hantavirus infections. Hence, efforts are required to develop a potent vaccine against the pathogen. The only vaccine that is in use for hantavirus is an inactivated virus vaccine, “Hantavax”, but it failed to produce neutralizing antibodies. Vaccine development is of much importance in dealing with the surge of hantavirus globally. In this study, hantavirus five proteins (N protein, G1 and G2, L protein, and non-structural proteins) were used in NetCTL 1.2 program to predict T-cell epitopes. To predict major histocompatibility complex (MHC) binding alleles, an immune epitope database (IEDB) was used. All predicted epitopes were then investigated for different immunoinformatics analyses such as antigenicity and toxicity analyses. The good water-soluble, non-toxic, probable antigenic, and DRB*0101 binder was selected. A multi-epitopes-based vaccine designing was then done where linkers were used to connect the shortlisted epitopes. In addition, an adjuvant molecule was supplementary to the multi-epitopes peptide to improve the vaccine’s immunogenic potential. The final vaccine construct’s three-dimensional structure was modeled by ab initio method. The vaccine molecule was then evaluated for its binding potential with TLR-3 immune receptor, which is key for its recognition and processing by the host immune system. Docking studies were performed using HADDOCK software. The best-docked complex was selected and visualized for intermolecular binding and interactions using UCSF Chimera 1.16 software. The findings revealed that the designed vaccine might be a potential vaccine against hantavirus and can be used in experimental animal model testings. Communicated by Ramaswamy H. Sarma

Emerging Maripa Hantavirus as a Potential Cause of a Severe Health Threat in French Guiana.

We describe the clinical parameters and management of nine confirmed cases of hantavirus pulmonary syndrome reported in French Guiana since 2008. All patients were admitted to Cayenne Hospital. Seven patients were men and the mean age was 48 years (range, 19-71 years). Two phases characterized the disease. The prodromal phase was characterized by fever (77.8%), myalgia (66.7%), and gastrointestinal symptoms (vomiting and diarrhea; 55.6%) starting, on average, 5 days before the illness phase, which was characterized by respiratory failure in all patients. Five patients died (55.6%) and the length of stay in the intensive care unit was 19 days (range, 11-28 days) for survivors. Detection of two back-to-back recent cases highlights the reason to screen for hantavirus infection during the nonspecific phase of the disease, in particular when concomitant pulmonary infection and digestive disorders are observed. Specific longitudinal serological surveys must also be used to identify other potential clinical forms of the disease in French Guiana.

Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission.

We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.

Deciphering the Hantavirus Host Range Combining Virology and Species Distribution Models with an Emphasis on the Yellow Pygmy Rice Rat (Oligoryzomys flavescens)

Hantaviruses are the causative agents of hantavirus pulmonary syndrome (HPS) in the Americas. In Central and South America, 28 hantavirus lineages were associated with different Sigmodontinae rodents. Of these, Lechiguanas hantavirus was initially described as a lineage associated with HPS cases in the central region of Argentina. Initial studies on the rodent hosts and viral lineages performed between 1999 and 2005 showed that HPS cases in Uruguay were distributed mostly in the southern region of the country, and that the Lechiguanas hantavirus (LECV) and the closely related Andes Central Plata hantaviruses were the viral lineages most frequently associated with HPS cases, both carried by the yellow pygmy rice rat (Oligoryzomys flavescens). Although these rodents are present all across the Uruguayan territory, determining the extent of the risk areas for hantavirus transmission based on the distribution of the infected rodents may be a useful tool for disease control and prevention. Distribution models are positioned as an effective instrument in the prediction of diseases affecting human health. Assessment of the potential distribution of rodent reservoir hosts and analysis of the influence of environmental factors on hantavirus transmission can help to understand the spatial patterns of disease transmission risk. In the present study, virological studies and species distribution models were integrated to understand the hantavirus infection risk pattern in Uruguay. Virological analyses confirmed that in Uruguay, the primary hantavirus reservoir host for both viral lineages is the yellow pygmy rice rat. Additionally, we report an Azara’s grass mouse (Akodon azarae) infected with the Andes Central Plata viral lineage. Based on the seropositive and nonseropositive yellow pygmy rice rats tested, the distribution models emphasized that favorable environmental conditions for the infected rodents are mainly related to the availability of human-disturbed rural environments with high humidity. We conclude that the innovative application of the methodologies reported herein allowed for the assessment of the current risk territory for HPS in Uruguay.

Hantavirus Infection in Children-A Pilot Study of Single Regional Center.

Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but the lower incidence in the pediatric population might also be related to a lack of diagnosis possibilities or even unsatisfactory knowledge about the disease. The purpose of this study was to evaluate the cases of hemorrhagic fever with renal syndrome diagnosed and treated in the Department of Nephrology at St. Mary's Emergency Hospital for Children in Iasi, Romania, representative of the North-East of Romania. We also reviewed the specialized literature on the topic. Between January 2017 and January 2022, eight cases of HFRS, all men, and seven from rural areas, aged 11-18 years old, were referred to our clinic because of an acute kidney injury (AKI). Seven cases were identified as Dobrava serotype while one case was determined by Haantan serotype. HFRS should always be considered as a differential diagnosis when faced with a patient with AKI and thrombocytopenia. Dobrava serotype is the most common hantavirus subtype in the Balkans. For the specific prevention of human infections, mainly in high-risk groups, vaccines are needed. As far as we know, this is the first study on HFRS in Romanian children.

Antigenic mapping and functional characterization of human New World hantavirus neutralizing antibodies.

Hantaviruses are high-priority emerging pathogens carried by rodents and transmitted to humans by aerosolized excreta or, in rare cases, person-to-person contact. While infections in humans are relatively rare, mortality rates range from 1 to 40% depending on the hantavirus species. There are currently no FDA-approved vaccines or therapeutics for hantaviruses, and the only treatment for infection is supportive care for respiratory or kidney failure. Additionally, the human humoral immune response to hantavirus infection is incompletely understood, especially the location of major antigenic sites on the viral glycoproteins and conserved neutralizing epitopes. Here, we report antigenic mapping and functional characterization for four neutralizing hantavirus antibodies. The broadly neutralizing antibody SNV-53 targets an interface between Gn/Gc, neutralizes through fusion inhibition and cross-protects against the Old World hantavirus species Hantaan virus when administered pre- or post-exposure. Another broad antibody, SNV-24, also neutralizes through fusion inhibition but targets domain I of Gc and demonstrates weak neutralizing activity to authentic hantaviruses. ANDV-specific, neutralizing antibodies (ANDV-5 and ANDV-34) neutralize through attachment blocking and protect against hantavirus cardiopulmonary syndrome (HCPS) in animals but target two different antigenic faces on the head domain of Gn. Determining the antigenic sites for neutralizing antibodies will contribute to further therapeutic development for hantavirus-related diseases and inform the design of new broadly protective hantavirus vaccines.

Protocols to Prevent Transmission of the Hantavirus Pulmonary Syndrome: Three Case Studies

The goal of the paper is to explain the risk posed by rodent contaminated materials and environments to cultural heritage professionals, to provide sound information from professional literature and reputable sources, to offer standardized protocols gleaned from these sources, and to view the protocols through case studies from three projects. By spelling out the affinity that rodents have for historic sites, museum collections, archives holdings, records repositories, library collections, and cultural heritage infrastructure it will be clear the risk is paramount. By making clear the widespread habitat of rodents that can spread viruses the case is made for wide adoption of protocols. Diverse professionals, working in conservation and allied fields, can utilize information in this paper as a starting point in planning projects to assess, handle, and treat rodent impacted items, storage areas, and sites.

Hantavirus Pulmonary Syndrome: 1993-2018.

From 1993 to 2018, hantavirus infections were reported in 39 states, with hantavirus pulmonary syndrome (HPS) as the most common and fatal manifestation. To identify differences in the presentation of HPS between children and adults, we hypothesized that children with HPS would be diagnosed later in their illness course given the nonspecific clinical features of HPS. This was an evaluation of the clinical and demographic characteristics of national HPS cases from 1993 to 2018. Data were from the Centers for Disease Control and Prevention database and 1 state department of health, comprising 97% of US cases. We compared children (0 to 12 years), adolescents (13 to 18 years), and adults using nonparametric and parametric analyses, with additional exploratory analyses to identify clinical variables associated with mortality. Among 719 HPS patients, 22 (3.0%) were aged ≤12 years, 47 (6.5%) were 13 to 18 years old, and the remaining 650 (90.4%) were adults. Overall mortality was 35.4% and did not differ between age groups (P = .8). The time between symptom onset and death differed by age group, with children living a median of 2 days (interquartile range [IQR] 2 to 3), adolescents 4 days (IQR 3 to 5), and adults 5 days (IQR 4 to 8; P = .001). The mean highest hematocrit and median highest creatinine level were significantly associated with mortality in those 0 to 18 years old but not adults. In our dataset representing the largest study of HPS in the United States, we found that children with HPS died more quickly than adults and that highest hematocrit and creatinine levels were associated with death only among those <19 years old.

A Brief History of Bunyaviral Family Hantaviridae.

The discovery of Hantaan virus as an etiologic agent of hemorrhagic fever with renal syndrome in South Korea in 1978 led to identification of related pathogenic and nonpathogenic rodent-borne viruses in Asia and Europe. Their global distribution was recognized in 1993 after connecting newly discovered relatives of these viruses to hantavirus pulmonary syndrome in the Americas. The 1971 description of the shrew-infecting Hantaan-virus-like Thottapalayam virus was long considered an anomaly. Today, this virus and many others that infect eulipotyphlans, bats, fish, rodents, and reptiles are classified among several genera in the continuously expanding family Hantaviridae.

Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus

The emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrug-resistant forms of the disease are prevalent, and there is currently no licensed commercial vaccine. Due to the numerous limitations of experimental vaccines, vaccines against various bacterial and viral diseases have developed via computational vaccine design. Several subtractive proteomics, immunoinformatics, docking, and simulation approaches were used in this study to develop a multi-epitope-based vaccine against Sin Nombre orthohantavirus. One possible antigenic protein-the glycoprotein precursor of surface glycoproteins (accession number >AAC42202.1)-was selected as a candidate for B cell-derived T cell epitopes mapping the detailed analysis of the core genome. Among the predicted epitopes, four epitopes (QVDWTKKSST, GLAASPPHL, SSYSYRRKLV, and MESGWSDTA), which were probably antigenic, nonallergenic, nontoxic, and water soluble, were used in the multi-epitope vaccine's construction. The shortlisted epitopes have the potency to cover 99.78% of the world's population, 97.93% of the Chinese population, and 97.36% of the Indian population. The epitopes were connected through AAY linkers and joined with >50S ribosomal adjuvant to enhance their efficacy. The vaccine comprises 182 amino acids with a molecular weight of 19.03770 kDa and an instability index of 26.52, indicating that the protein is stable. A molecular docking study revealed that the vaccine has a good binding affinity with TLR-4 and TLR-8, which is vital for inducing the immune system. Top-1 docked complexes of vaccine- TLR-4 and TLR-8 with the lowest binding energy of -12.52 kc/mol and -5.42 kc/mol, respectively, were considered for molecular dynamic simulation analysis. Furthermore, we predicted that the docked complexes are properly stable throughout simulation time in both normal mode and AMBER-based simulation analysis. The MMGBSA analysis calculated -122.17 and -125.4 net binding energies for the TLR-8- and TLR4-vaccine complexes, respectively, while the MMPBSA analysis estimated -115.63 and -118.19 for the TLR-8- and TLR4-vaccine complex, respectively, confirming that the binding stability with receptors is stable, which is important for inducing a strong response. However, the current work is computation-based, so experimental validation is highly recommended.

Trends and focuses of hantavirus researches: a global bibliometric analysis and visualization from 1980 to 2020

BackgroundThere have been worldwide changes in the researches on hantaviruses in the past several decades. Nevertheless, there are few bibliometric analysis studies this field. We aim to evaluate and visualize the research focuses and trends of this field using a bibliometric analysis way to help understand the developmet and future hotspots of this field.Material and methodsPublications related to hantavirus studies were culled from the Web of Science Core Collection to generate trend analysis. The articles and reviews were re-extracted and Countries, institutions, authors, references and keywords in this field were visually analyzed by using VOSviewer and CiteSpace.ResultsA total of 4408 studies were included and the number of publications regarding hantaviruses significantly increased yearly. Three thousand seven hundred sixteen research articles and reviews were retrieved to generate bibliometric analysis. These studies mainly come from 125 countries led by USA and China and 3312 institutions led by the University of Helsinki. Twelve thousand five hundred twenty nine authors were identified and Vaheri A were the most influential author. Journal of Virology was the journal with the most studies and citations. After analysis, Hemorrhagic fever with renal syndrome, Hantavirus cardiopulmonary syndrome, nephropathia epidemica and related genotypes, clinical symptoms and rodents were the most common keywords and developing areas.ConclusionResearch on hantavirus is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future. The ecology and clinical symptoms of new genotypes, the vaccine development and factors that affect host population distribution and density are current and developing areas of study.

Favipiravir in the Battle with Respiratory Viruses.

Among antiviral drugs, the vast majority targets only one or two related viruses. The conventional model, one virus - one drug, significantly limits therapeutic options. Therefore, in the strategy of controlling viral infections, there is a necessity to develop compounds with pleiotropic effects. Favipiravir (FPV) emerged as a strong candidate to become such a drug. The aim of the study is to present up-to-date information on the role of favipiravir in the treatment of viral respiratory infections. The anti-influenza activity of favipiravir has been confirmed in cell culture experiments, animal models, and clinical trials. Thoroughly different - from the previously registered drugs - mechanism of action suggests that FVP can be used as a countermeasure for the novel or re-emerging influenza virus infections. In recent months, favipiravir has been broadly investigated due to its potential efficacy in the treatment of COVID-19. Based on preclinical and clinical studies and a recently published meta-analysis it seems that favipiravir may be a promising antiviral drug in the treatment of patients with COVID-19. FPV is also effective against other RNA respiratory viruses and may be a candidate for the treatment of serious infections caused by human rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza viruses and hantavirus pulmonary syndrome.

Dihydropyridine-derived calcium channel blocker as a promising anti-hantavirus entry inhibitor.

Hantaviruses, the causative agent for two types of hemorrhagic fevers, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are distributed from Eurasia to America. HFRS and HPS have mortality rates of up to 15% or 45%, respectively. Currently, no certified therapeutic has been licensed to treat hantavirus infection. In this study, we discovered that benidipine hydrochloride, a calcium channel blocker, inhibits the entry of hantaviruses in vitro. Moreover, an array of calcium channel inhibitors, such as cilnidipine, felodipine, amlodipine, manidipine, nicardipine, and nisoldipine, exhibit similar antiviral properties. Using pseudotyped vesicular stomatitis viruses harboring the different hantavirus glycoproteins, we demonstrate that benidipine hydrochloride inhibits the infection by both HFRS- and HPS-causing hantaviruses. The results of our study indicate the possibility of repurposing FDA-approved calcium channel blockers for the treatment of hantavirus infection, and they also indicate the need for further research in vivo.

Modelling relative abundance of Oligoryzomys flavescens, an Orthohantavirus reservoir, in an endemic hantavirus pulmonary syndrome zone.

Hantavirus pulmonary syndrome (HPS) is a zoonotic emerging infectious disease caused by New World orthohantaviruses (family Hantaviridae) hosted by rodents of the family Cricetidae. In Argentina, one of its main hosts is the sigmodontine rodent Oligoryzomys flavescens, a widely distributed mouse of the Pampas, Delta and Espinal ecoregions of central-east Argentina. Because the abundance of the reservoir and its proportion in the rodent community affects both virus prevalence and human exposure risk, its estimation throughout its known geographical distribution is of key importance for the design of public health strategies to prevent HPS. The aim of this study was therefore to model the relative abundance of O.flavescens in most of the Pampas ecoregion within Buenos Aires Province, Argentina, where hantavirus pulmonary syndrome is endemic. To do this we used owl-pellet samples collected between 2006 and 2008 from 51 sites distributed throughout most of Buenos Aires province. Mammalian prey in each pellet was identified to the lowest possible taxonomic level by examination of the skulls, dentaries and molars. We modelled the frequency of O.flavescens found in each sample as a function of climatic, environmental, and topographic data of each site. The two best models were applied to a Geo referential Information System to build maps of estimated frequency (as a proxy of relative abundance) within Buenos Aires province. Estimated relative abundance of O.flavescens in Buenos Aires province was significantly associated with annual mean temperature, annual precipitation and presence of freshwater bodies, and varied among sub-regions, with the Inland and Rolling Pampas being the regions with highest frequencies. Knowing in which areas O.flavescens abundance is expected to be higher can be used to concentrate limited sanitary efforts in those areas that are most needed in order to reduce transmission and increase detection.

In Silico Phytochemical Screening for Hantavirus

&#x0D; &#x0D; Several rodent species are carriers of hantavirus which are present throughout the world. Hantavirus was a group of unknown class of viruses which was first seen in the United States of America in 1993 as an acute respiratory disease now termed hantavirus pulmonary syndrome (HPS). Earlier HPS hantavirus were known as the agents of hemorrhagic fever with renal syndrome which was seen in eastern hemisphere of the world .A lot of research is going around in and around hantavirus Their ubiquity and potential for causing severe human illness make these viruses an important public health concern.We present a docking based screening using a quantum mechanical scoring of a library built from approved drugs and compound that limonin ,curcumin, luteolin, rutin, Baicalin, Quercetin, Resveratrol, Kaempferol, Naringenin, Atropine, 4 Hydroxy Coumarin, Colchicine, Thymoquinone, Glabridin ,Hypericin, Lycorine with proteins having PDB id’s 5E04 and 5E05 could display that the phytochemicals can act against Hantavirus. We hope that our findings may contribute to rational drug design against Hantavirus.&#x0D; &#x0D;

Hantavirus Pulmonary Syndrome Coexistent with Dengue

Dengue is an arthropod-borne disease caused by viruses of Flaviviridae family. It poses a major public health burden in tropical and sub-tropical regions. Clinical features of dengue vary from a mild flu-like disease and rash, to a potentially lethal haemorrhagic fever or shock syndrome. Hantavirus pulmonary syndrome is a rodent-born disease emerging in the American continent and is caused by viruses of the Bunyaviridae family. Potential reservoirs of these agents were described in Brazilian Central Plateau. Dengue infection is transmitted by mosquitoes, while hantaviruses are acquired by contact or inhalation of aerosolised excreta of infected rodents. Dengue and hantavirus infections have also been considered as emerging public health problems in some Indian areas; moreover, other infections mixed with dengue have been documented. The case of a Brazilian patient with hantavirus pulmonary syndrome and serologic evidence of dengue infection is described.

Screening and identification of HTNVpv entry inhibitors with high-throughput pseudovirus-based chemiluminescence

Hantaviruses, such as Hantaan virus (HTNV) and Seoul virus, are the causative agents of Hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS), and are important zoonotic pathogens. China has the highest incidence of HFRS, which is mainly caused by HTNV and Seoul virus. No approved antiviral drugs are available for these hantaviral diseases. Here, a chemiluminescence-based high-throughput-screening (HTS) assay was developed and used to screen HTNV pseudovirus (HTNVpv) inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine sources. We identified six compounds with in vitro anti-HTNVpv activities in the low-micromolar range (EC50 values of 0.1–2.2 ​μmol/L; selectivity index of 40–900). Among the six selected compounds, cepharanthine not only showed good anti-HTNVpv activity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 ​h after infection by 94% (180 ​mg/kg/d, P ​< ​0.01), 93% (90 ​mg/kg/d, P ​< ​0.01), or 92% (45 ​mg/kg/d, P ​< ​0.01), respectively, in a bioluminescent imaging mouse model. A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry phases. Overall, we have established a HTS method for antiviral drugs screening, and shown that cepharanthine is a candidate for HCPS and HFRS therapy. These findings may offer a starting point for the treatment of patients infected with hantaviruses.

Effects of Viral Infection on Endothelial Activation and Barrier Function

Endothelial cells (ECs) are in the inner layer of blood vessels, and it controls the transportation of nutrition and essential molecules from the extracellular matrix to the intracellular space making a homeostasis environment. Vascular endothelium can be disrupted with viruses, which are among the main reasons for epidemic and pandemic outbreaks, and it leads to health issues such as cardiovascular‐related diseases. Wide range of viruses can potentially target the endothelium including Dengue virus estimated to infect 390 million people per year. Zika virus leads to pregnancy complications such as preterm birth and miscarriage. Tick‐borne encephalic damaged the central nervous system and, Hantavirus has a mortality rate of 38% through hantavirus pulmonary syndrome. Reviewing these several diseases, including SARS‐CoV‐2, has given an in‐depth look at what the endothelial cells are going through when these viruses are infecting the host bodies. Following the virus infection, ECs are going through activation mode, which is accompanied with glycocalyx degradation, plasma leakage, phosphorylation of P120, and cadherin, increased proinflammatory responses and, disruption of barrier integrity.The SARS‐CoV‐2 pandemic has taken a global toll; With a total of 362 million cases, there are 5.63 million deaths occurring. With the usage of immunofluorescence and vascular permeability assay, we monitor how Human Umbilical Vascular Endothelial Cells (HUVEC) and Human Lung Microvascular Endothelial Cells (HLMVEC) are impacted when treated with UV‐inactivated & heat‐inactivated SARS‐CoV‐2, and tumor necrosis factor (TNF)‐α. TNF‐α is an inflammatory cytokine prominent during inflammation and its known to increase the permeability of endothelium. Like the TNF‐α, both cells treated with UV‐inactivated and heat‐inactivated SARS‐CoV2 demonstrated boosted permeability. With the considerable effect of SARS‐CoV2 on the permeability of ECs, it is essential to understand the mechanisms and pathways behind the boosted leak, including the impact of the virus on the expression of adhesion molecules like platelet endothelial cell adhesion molecule (PECAM‐1). One can see in the images of HUVEC and HLMVEC that SARS‐CoV‐2 diminish the localization of PECAM‐1. On a non‐treated negative control, cells are spaced evenly and are close to another since their junctions are not targeted. Once the cells are treated with either heat‐inactivated or UV‐inactivated SARS‐CoV‐2, PECAM‐1 localization is disrupted, which can be seen from the space between cells since the PECAM‐1 has been altered and is no longer holding the cells together. From those exact images, one can detect the enlarged and irregular shapes of nucleuses and change in morphology of these cells since the SARS‐CoV‐2 is not only altering the PECAM‐1 complex but it can also modify various proteins and mRNAs. By combining information of various viruses and knowledge from our studies, we can understand the mechanisms of ECs and take measurements to protect ECs from viruses. In future experiments, we will detect if the PECAM‐1 expression is lowered when treated with SARS‐CoV‐2 and TNF‐α or if PECAM‐1 is internalized in the cell. Moreover, we can do mRNA and immunoblotting analysis to elaborate the changes in protein pathways as a consequence of COVID‐19.