Langya henipavirus: Is it a potential cause for public health concern?

A new virus, named Langya henipavirus (LayV), has recently been identified in Shandong and Henan provinces in China and has so far infected 35 individuals between April 2018 and August 2021. It is closely related to other known henipaviruses (Nipah and Hendra viruses) that can cause up to 70% human case fatality. Even though LayV has not been shown to be fatal in humans and does not appear to be transmitted from human-to-human, it is an RNA virus with the capacity to evolve genetically in the infected hosts (e.g. shrews) and can infect humans (e.g. farmers who have been in close contacts with shrews). It is therefore important to be vigilant about this new viral outbreak.

An Overview of Anthropogenic Actions as Drivers for Emerging and Re-Emerging Zoonotic Diseases.

Population growth and industrialization have led to a race for greater food and supply productivity. As a result, the occupation and population of forest areas, contact with wildlife and their respective parasites and vectors, the trafficking and consumption of wildlife, the pollution of water sources, and the accumulation of waste occur more frequently. Concurrently, the agricultural and livestock production for human consumption has accelerated, often in a disorderly way, leading to the deforestation of areas that are essential for the planet's climatic and ecological balance. The effects of human actions on other ecosystems such as the marine ecosystem cause equally serious damage, such as the pollution of this habitat, and the reduction of the supply of fish and other animals, causing the coastal population to move to the continent. The sum of these factors leads to an increase in the demands such as housing, basic sanitation, and medical assistance, making these populations underserved and vulnerable to the effects of global warming and to the emergence of emerging and re-emerging diseases. In this article, we discuss the anthropic actions such as climate changes, urbanization, deforestation, the trafficking and eating of wild animals, as well as unsustainable agricultural intensification which are drivers for emerging and re-emerging of zoonotic pathogens such as viral (Ebola virus, hantaviruses, Hendravirus, Nipah virus, rabies, and severe acute respiratory syndrome coronavirus disease-2), bacterial (leptospirosis, Lyme borreliosis, and tuberculosis), parasitic (leishmaniasis) and fungal pathogens, which pose a substantial threat to the global community. Finally, we shed light on the urgent demand for the implementation of the One Health concept as a collaborative global approach to raise awareness and educate people about the science behind and the battle against zoonotic pathogens to mitigate the threat for both humans and animals.

Bat and bat-borne hantaviruses

Hantaviruses are important pathogenes of natural focal diseases that causes hemorrhagic fever with renal syndrome and Hantavirus pulmonary syndrome. According to the latest classification of the International Committee on Taxonomy of Viruses, hantaviruses can be divided into 53 species, 7 genera, and 4 subfamilies. Hantaviruses are widely found in Rodentia, Chiroptera, and Insectivora, and later also found in reptile, Actinopterygii, and Agnatha. There are many species of bats, which are the second largest group of mammals in the world after rodents. At present, 1 446 species have been reported, accounting for about 22% of global mammals. In addition, bats have strong flight ability and are widely distributed in all continents except Antarctica. As the host animal of viruses, bats bear a variety of viruses, and many emerging infectious pathogens such as Marburg virus, Hendra virus, and Nipah virus have been confirmed to come from bats. Bats have also been associated to Ebola virus, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2. In recent decades, more and more bat-borne hantaviruses have been discovered. Bats and bat-borne hantaviruses have an important research value. Therefore, this paper reviews the latest classification of Hantavirus and bat-borne hantaviruses.

Climate Anomalies and Spillover of Bat-Borne Viral Diseases in the Asia-Pacific Region and the Arabian Peninsula.

Climate variability and anomalies are known drivers of the emergence and outbreaks of infectious diseases. In this study, we investigated the potential association between climate factors and anomalies, including El Niño Southern Oscillation (ENSO) and land surface temperature anomalies, as well as the emergence and spillover events of bat-borne viral diseases in humans and livestock in the Asia-Pacific region and the Arabian Peninsula. Our findings from time series analyses, logistic regression models, and structural equation modelling revealed that the spillover patterns of the Nipah virus in Bangladesh and the Hendra virus in Australia were differently impacted by climate variability and with different time lags. We also used event coincidence analysis to show that the emergence events of most bat-borne viral diseases in the Asia-Pacific region and the Arabian Peninsula were statistically associated with ENSO climate anomalies. Spillover patterns of the Nipah virus in Bangladesh and the Hendra virus in Australia were also significantly associated with these events, although the pattern and co-influence of other climate factors differed. Our results suggest that climate factors and anomalies may create opportunities for virus spillover from bats to livestock and humans. Ongoing climate change and the future intensification of El Niño events will therefore potentially increase the emergence and spillover of bat-borne viral diseases in the Asia-Pacific region and the Arabian Peninsula.

Henipavirus Immune Evasion and Pathogenesis Mechanisms: Lessons Learnt from Natural Infection and Animal Models.

Nipah henipavirus (NiV) and Hendra henipavirus (HeV) are zoonotic emerging paramyxoviruses causing severe disease outbreaks in humans and livestock, mostly in Australia, India, Malaysia, Singapore and Bangladesh. Both are bat-borne viruses and in humans, their mortality rates can reach 60% in the case of HeV and 92% for NiV, thus being two of the deadliest viruses known for humans. Several factors, including a large cellular tropism and a wide zoonotic potential, con-tribute to their high pathogenicity. This review provides an overview of HeV and NiV pathogenicity mechanisms and provides a summary of their interactions with the immune systems of their different host species, including their natural hosts bats, spillover-hosts pigs, horses, and humans, as well as in experimental animal models. A better understanding of the interactions between henipaviruses and their hosts could facilitate the development of new therapeutic strategies and vaccine measures against these re-emerging viruses.

Discovery of Potential Antiviral Compounds against Hendra Virus by Targeting Its Receptor-Binding Protein (G) Using Computational Approaches.

Hendra virus (HeV) belongs to the paramyxoviridae family of viruses which is associated with the respiratory distress, neurological illness, and potential fatality of the affected individuals. So far, no competitive approved therapeutic substance is available for HeV. For that reason, the current research work was conducted to propose some novel compounds, by adopting a Computer Aided Drug Discovery approach, which could be used to combat HeV. The G attachment Glycoprotein (Ggp) of HeV was selected to achieve the primary objective of this study, as this protein makes the entry of HeV possible in the host cells. Briefly, a library of 6000 antiviral compounds was screened for potential drug-like properties, followed by the molecular docking of short-listed compounds with the Protein Data Bank (PDB) structure of Ggp. Docked complexes of top two hits, having maximum binding affinities with the active sites of Ggp, were further considered for molecular dynamic simulations of 200 ns to elucidate the results of molecular docking analysis. MD simulations and Molecular Mechanics Energies combined with the Generalized Born and Surface Area (MMGBSA) or Poisson-Boltzmann and Surface Area (MMPBSA) revealed that both docked complexes are stable in nature. Furthermore, the same methodology was used between lead compounds and HeV Ggp in complex with its functional receptor in human, Ephrin-B2. Surprisingly, no major differences were found in the results, which demonstrates that our identified compounds can also perform their action even when the Ggp is attached to the Ephrin-B2 ligand. Therefore, in light of all of these results, we strongly suggest that compounds (S)-5-(benzylcarbamoyl)-1-(2-(4-methyl-2-phenylpiperazin-1-yl)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide and 5-(cyclohexylcarbamoyl)-1-(2-((2-(3-fluorophenyl)-2-methylpropyl)amino)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide could be considered as potential therapeutic agents against HeV; however, further in vitro and in vivo experiments are required to validate this study.

From Protein to Pandemic: The Transdisciplinary Approach Needed to Prevent Spillover and the Next Pandemic.

Pandemics are a consequence of a series of processes that span scales from viral biology at 10-9 m to global transmission at 106 m. The pathogen passes from one host species to another through a sequence of events that starts with an infected reservoir host and entails interspecific contact, innate immune responses, receptor protein structure within the potential host, and the global spread of the novel pathogen through the naive host population. Each event presents a potential barrier to the onward passage of the virus and should be characterized with an integrated transdisciplinary approach. Epidemic control is based on the prevention of exposure, infection, and disease. However, the ultimate pandemic prevention is prevention of the spillover event itself. Here, we focus on the potential for preventing the spillover of henipaviruses, a group of viruses derived from bats that frequently cross species barriers, incur high human mortality, and are transmitted among humans via stuttering chains. We outline the transdisciplinary approach needed to prevent the spillover process and, therefore, future pandemics.

Cospeciation of coronavirus and paramyxovirus with their bat hosts in the same geographical areas.

BACKGROUND: Bat-borne viruses are relatively host specific. We hypothesize that this host specificity is due to coevolution of the viruses with their hosts. To test this hypothesis, we investigated the coevolution of coronavirus and paramyxovirus with their bat hosts. Published nucleotide sequences of the RNA-dependent RNA polymerase (RdRp) gene of 60 coronavirus strains identified from 37 bat species, the RNA polymerase large (L) gene of 36 paramyxovirus strains from 29 bat species, and the cytochrome B (cytB) gene of 35 bat species were analyzed for coevolution signals. Each coevolution signal detected was tested and verified by global-fit cophylogenic analysis using software ParaFit, PACo, and eMPRess. RESULTS: Significant coevolution signals were detected in coronaviruses and paramyxoviruses and their bat hosts, and closely related bat hosts were found to carry closely related viruses. CONCLUSIONS: Our results suggest that paramyxovirus and coronavirus coevolve with their hosts.

Nipah@20: Lessons Learned from Another Virus with Pandemic Potential.

Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential.