Nipah is an infectious negative-sense single-stranded RNA virus which belongs to the genus henipavirus and family Paramyxoviridae . It is a pleomorphic enveloped virus with a particle size ranging from 40 to 1,900 nm . While fruit bats are thought to be the natural reservoirs of the virus, they are also able to spread to humans and some other species . There are two major genetic lineages of the virus which are known to infect humans i.e, NIV Malaysia (NIVM) and NIV Bangladesh (NIVB) .
The first outbreak of Nipah virus infection erupted between September 29,1998, and April 4, 1999, when cases of febrile encephalitis in the suburb of Ipoh, Perak, Southern Peninsular Malaysia were reported to the Malaysian Ministry of Health (MOH) . It was traced back to cross-species transmission of the virus from pigs to humans [4, 5]. In 2001 another strain of the virus was reported to cause an outbreak in Meherpur, Bangladesh. Since then outbreaks have been recorded almost annually in the country and surrounding regions such as Siliguri, India [6, 7]. Most of the outbreaks have been observed to have a mortality rate ranging from 50–100% . Although direct contact with the infected bat’s contaminants could cause transmission of the virus, direct human-to-human transmission has also been observed in the case of healthcare professionals and relatives of infected patients [9, 10]. More recently, the virus has garnered attention due to the first-ever outbreak in southern India during May of 2018 where 19 cases of NiV were reported in Kozhikode, Kerala. In the subsequent year, 2019, another case was reported in Ernakulam district of the state [11, 12].
Nipah virus causes cell-to-cell fusion in the host thus forming multinucleated cells called syncytia. This allows the virus to spread despite the absence of viral budding and greatly influences its pathogenicity [13, 14]. The incubation period of the virus ranges from 5 to 14 days (https://www.cdc.gov/vhf/nipah/pdf/factsheet.pdf). Primarily the virus infects the central nervous system but the NIVB strain has been shown to have significant respiratory involvement . High mutation rate, human to human transmission, survival time of up to 4 days under various environmental conditions and lack of treatment makes it a potential bioterrorism agent [15, 16].
Currently, there is no known treatment for the disease. Broad-spectrum antiviral ribavirin has shown contradictory results with even the most optimistic ones significantly below 50% in causing reduction of the mortality rate [17, 18, 19]. Favipiravir (T-705), a purine analogue antiviral, is reported to provide protection to upto 14 days in the Syrian hamster model challenged with a lethal dose of Nipah virus . More recently, experimental drug remdesivir has demonstrated complete protection to four African green monkeys who received a lethal dose of Nipah virus. Studies are planned to assess the efficacy of the treatment over time . Despite being a lethal pathogen there is not a single drug under clinical trial against this virus. Due to several challenges in discovery and development of NVIs, along with lack of therapeutic intervention and the pathogenic propensity of the virus, Nipah infections are enlisted amongst WHO’s list of priority diseases .
As mentioned above, various groups have made efforts over the years to identify Nipah virus inhibitors using a variety of viral assays. Most of them have used syncytia formation or titre reduction assays to identify Nipah virus inhibitors. Some of the earlier studies report nipah inhibitors based on screening of large libraries within BSL-4 settings to identify compounds that inhibited the virus-induced cytopathic effect. Three sulfonamide compounds with low EC50 values are reported  from these screens. More recently, Bimolecular Multicellular Complementation assays have been developed which can be used to identify potential anti-nipah inhibitors by qualitatively and quantitatively investigating the formation of a syncytium . Also reported recently is a humanized monoclonal antibody for cross-neutralizing NiV and HeV. Cryo-electron microscopy followed by fusion studies demonstrated that the antibody binds to a prefusion-specific quaternary epitope which is conserved in NiV F and HeV F glycoproteins. The binding prevents membrane fusion and viral entry and clearly indicates the importance of the HNV prefusion F conformation for eliciting a robust immune response .
Despite reports of nipah virus inhibitors, no systematic evaluation of the reported compounds is performed. A few antiviral inhibitor databases and studies exist, namely, The Influenza Research Database (IRD) , The Virus Pathogen Database and Analysis Resource (ViPR) , enamine library (https://enamine.net/hit-finding/focused-libraries/view-all/antiviral-library), etc. They contain very limited or no information with the focus on Nipah virus. The ones with focus on Nipah virus inhibitors are either scattered datasets or curated versions with limited or no evaluation of the anti-Nipah compounds as starting points for drug discovery and development of anti-Nipah inhibitor(s) .
Towards this, we developed a combined evidence based strategy to systematically evaluate Nipah virus inhibitors. With this objective, we curated the anti-Nipah compounds using a crowdsourcing model and the data were made publicly available at – http://vinodscaria.rnabiology.org/nipah since the inception of the project (May 2018). Our two pronged strategy comprised of (i) prioritization of NVIs based on the robustness of the assays which were used to identify them and (ii) estimation of several drug likeness parameters for the NVIs. The drug likeness analysis includes diversity analysis, similarity to FDA approved compounds (as drug repurposing candidates) or reported antivirals (to identify new scaffolds), profiling based on PAINS and DruLito filters and comparison to ZINC lead like libraries. The data curated from literature along with all these analyses is made available on a web-based platform which also allows submission and assessment of new molecules reported as NVIs.