Nipah virus (NiV) was originally identified during an outbreak in Malaysia in 1999, was associated with the Hendra virus in the Paramyxoviridae group [1]. Since then, sporadic NiV outbreak outbreaks have been reported in several countries, including the latest in Indian Kerala [2]. NiV is endemic, highly pathogenic, and can infect most species of mammals. Henipavirus natural reservoirs seem to be Pteropus-type fruit bats [3]. However, NiV has a wide range of hosts, such as humans[4] which lead to serious neurological, respiratory, and cardiovascular illnesses. Hosts include horses, dogs, dogs, pigs, cats, and hamsters. Since NiV can be passed from zoonotic to human routes, the risk for outbreaks is very high [5]. Particularly, The NiV outbreaks are the most prominent for human-to-human transmission. About 600 cases of NiV human infections were reported between 1998 and 2015, where the fatality rate in Malaysia was 38% and 43–100% in India and Bangladesh [2].
Due to its persistent pathogenicity, high mortality, and lack of effective therapeutics against its infection, NiV is a biosafety level 4 (BSL4) pathogen [6]. Some efforts have been made to manage NiV in the search for small molecular therapy for various structural proteins [7], [8]. Favipiravir has been shown to combat viral reproduction and transcription in NiV and HeV in a recent in vitro study; [9]. Also reported was R1479 (4′-azidocytidine) to inhibit various family members of Paramyxoviridae [10]. Nevertheless, no approved medicines are yet available for efficient human usage despite these efforts to develop such inhibitors. While Ribavirin is not an established NiV treatment, it is especially used in a state of emergency as a first-line treatment strategy for acute NiV encephalitis [11]; It does however have different side effects during NiV therapy, such as nausea, vomiting, and convulsions [12]. Known for treating NiV, small molecules inhibit host proteins such as Interferon Regulatory Factor 3 and RIG-I-like receptors which contribute innate immune system [13]. No approved therapeutics are available to efficiently use in humans despite these efforts to develop such inhibitors. Therefore, the definition of potential NiV inhibitors is an eminent requirement. Various efforts were made to manage NiV infection by looking for small molecular therapy for various structural proteins [7], [8], [14], [15].
The structure of the NiV virus is a parallel, long, coiled-coil, tetrameric with a small helical cap as tethers of the viral polymerase to nucleocapsid and multimeric phosphoprotein. Nipah virus has a single-stranded, negative-sense RNA genome that is encapsulated by the nucleoprotein (N) and transcribed and replicated by the polymerase protein (L). Hence molecular inhibition of RNA polymerase is one of the prime strategies for treating NiV infection. Also, as an effective strategy to interrupt virus adhesion with the host, the inferences regarding inhibition of interactions between RNA polymerase and RNA, which provide the structural basis for screening antiviral therapeutic inhibitors against NiV.
The most reliable and widely used approach in the early stages of drug discovery is structure-based molecular docking [16]; However, information on their potential side effects leading to almost 30 percent failure of the drug applicants due to toxicity or clinical safety problems is not generally taken into account [17]. The drug's off-target toxicity and chemical structure that leads to its non-optimal efficacy[18] is predicted to cause these side effects [19]. There is therefore no understanding of the assessment of drug toxicity at the level of molecular interaction relying only on this method. Different approaches should be used to control any possible pandemic of Nipah virus such as using machine learning for detection of different strains [20], [21], early detection of respiratory syndromes[22], and developing new drugs or scanning for possible molecule that may target and inhibit viral life cycle [22].
This is linked to the observation that interactions between drugs and their direct target frequently lead to differential expressions of downstream target regulated genes (Noh, Shoemaker, & Gunawan, 2018), which cause potential activation, repression, or dysregulation of downstream pathways. Here we introduce a molecular docking study for fourteen possible molecules and drug may act against RNA-dependent RNA polymerase of Nipah virus. Some previously efforts developed vaccine based on analysis of the whole proteome[23].