Advancing public health preparedness:Establishment of Nipah virus molecular diagnostic test at the National Reference Laboratory,Sri Lanka

Objective:To establish Nipah virus diagnostic capabilities at the National Reference Laboratory in Sri Lanka using the NIV Pune real-time PCR kit.Methods:Strict safety precautions were adhered during testing due to the high pathogenicity of the Nipah virus,with all diagnostics conducted in a BSL2+laboratory at the Medical Research Institute in Sri Lanka.RNA extraction was performed using the QIAamp Viral RNA Mini kit.The NIV Pune in-house real-time PCR kit was employed,following established primer/probe sequences and controls.The assay was validated using the Rotor-Gene Q Series Real-time PCR platform.Results:The validation run of the Nipah virus real-time PCR test demonstrated robust performance,with positive controls consistently detecting Nipah RNA at a Ct value of 21.50±0.01.Negative controls confirmed assay specificity with an external negative control which was also used as an extraction control and showed no interference.The internal control exhibited stable behavior,enhancing confidence in PCR results.The qPCR analysis graph illustrated the successful detection of internal and positive controls,validating the reliability of the assay.Conclusions:Establishing Nipah virus diagnostic capabilities in Sri Lanka signifies a proactive and collaborative response to the persistent global health threat.

Nipah Virus Unveiled: A Review Article

Nipah virus (NiV) is a highly infectious zoonotic pathogen that poses a significant threat to human and animal health. First identified in Malaysia in 1998, NiV has since caused several outbreaks in Southeast Asia, with sporadic cases reported in Bangladesh and India. The virus is primarily transmitted to humans through direct contact with infected animals, primarily fruit bats, or through the consumption of contaminated fruits and their juices. NiV infection presents a wide spectrum of clinical features, ranging from mild respiratory illness to severe encephalitis, with a high case fatality rate. The incubation period typically ranges from 4 to 14 days, during which patients develop fever, headache, myalgia, and respiratory symptoms such as cough and sore throat. As the disease progresses, neurological signs become prominent, including altered consciousness, seizures, and focal deficits. Severe cases may exhibit acute respiratory distress syndrome and multi organ failure. Laboratory findings often include lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Diagnosis of NiV infection requires specialized laboratory testing, including reverse transcription-polymerase chain reaction (RT-PCR) and serological assays. Currently, no specific antiviral treatment exists for NiV infection, and management primarily focuses on supportive care. Prevention and control strategies encompass public health interventions, surveillance, and raising awareness among healthcare providers and the general population. The emergence and re-emergence of NiV highlight the urgent need for continued research, improved diagnostic capabilities, and the development of effective vaccines and therapeutics to mitigate the impact of this deadly virus.

Mathematical Analysis of Nipah Virus Infections Using Optimal Control Theory

The optimal use of intervention strategies to mitigate the spread of Nipah Virus (NiV) using optimal control technique is studied in this paper. First of all we formulate a dynamic model of NiV infections with variable size population and two control strategies where creating awareness and treatment are considered as controls. We intend to find the optimal combination of these two control strategies that will minimize the cost of the two control measures and as a result the number of infectious individuals will decrease. We establish the existence for the optimal controls and Pontryagin’s maximum principle is used to characterize the optimal controls. The numerical simulation suggests that optimal control technique is much more effective to minimize the infected individuals and the corresponding cost of the two controls. It is also monitored that in the case of high contact rate, controls have to work for longer period of time to get the desired result. Numerical simulation reveals that the spread of Nipah virus can be controlled effectively if we apply control strategy at early stage.

Nipah Virus: A Zoonotic Virus Transmitted from Bats and Pigs, Causing an Epidemic in Southeast Asia

Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an almost 50% death rate. The virus is transmitted through direct contact with contaminated subjects and infecting the human respiratory system. Ephrin B2 and B3, the surface glycoproteins on the host cell, have been the primary and the most effective route for viral entrance. Binding with viral surface G protein, the F protein triggers, enabling viral-host fusion. Until now, NiV vaccines are not yet available in the public market, however, preventions such as avoiding direct contact and masking are advised.

Preventing the Re-emergence of Deadly Nipah Virus

The Indo-Bangladesh region frequently suffers from periodic Nipah virus(NiV)outbreaks.NiV is a zoonotic agent that can be transmitted from animals to humans and also from humans to humans.NiV infections may cause deadly neurological dysfunctions with a fatality rate of up to 75%.Various methods have been developed to diagnose NiV infections at different stages of the disease,but there is currently no specific antiviral treatment or vaccine available.NiV outbreaks are mostly endemic;however,the high susceptibility of the human population,high mutation rates of the viral RNA genome and the possibility of human-to-human transmission in this era of globalization enable NiV to potentially cause a pandemic.To prevent serious consequences of NiV outbreaks,international deliberation on risk assessment,investigation of the molecular and genetic aspects of NiV,pertinent measures of surveillance and framing of general guidelines for its management should be integrated.This review underlines the basic information available in the literature and its application for further research to reach a solution for mitigation of such catastrophic infections.

In silico identification and characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses

Objective: To explore a common B-and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus(He V) and Nipah virus(Ni V). Methods: Membrane proteins F, G and M of He V and Ni V were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B-and T-cell epitopes that shared maximum identity with He V and Ni V were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico. Results: One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope(VDPLRVQWRNNSVIS) showed at least 66% identity with all Ni V and He V G protein sequences, while the 15-mer M-epitope(GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all Ni V and He V M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II(MHC II) and class-I(MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response. Conclusions: Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against He V and Ni V. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.

Outbreak of an emerging zoonotic Nipah virus:An emerging concern

The Nipah virus(NiV)infection is one of the newly emerging deadly zoonotic diseases which carries a significant weightage of mortality among its victims.Due to the relatively recent history of its emergence and only a few known outbreaks,we cannot predict but foresee its potential to create havoc,which can be far more dreadful than the current ongoing COVID-19 pandemic.Here we have tried to depict the fatal potential of the virus and the increased propensity with which it can spread to rest of the world.

Human Monoclonal Antibodies as Candidate Therapeutics Against Emerging Viruses and HIV-1

More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics.

The Mechanism of Henipavirus Fusion:Examining the Relationships between the Attachment and Fusion Glycoproteins

The henipaviruses,represented by Nipah virus and Hendra virus,are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia,Southeast Asia,India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins;efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion(F) glycoprotein. The analysis of monoclonal antibody(mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein,which is a tetrameric oligomer,and not with soluble forms of G(sG) ,which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably,these mutants of G also appear to confer a post-receptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together,these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further,receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.