Since early times, humans have been confronted with numerous microbial infections due to the adaptibilty in varying environmets. The pathogens of viral and bacterial nature have been encountered multiple times in the last couple of centuries. These pathogens often diffuse into the populations very rapidly and thus resulting in human deaths at a large scale (Christou, 2011). It doesn’t take much time for a small pathogenic outbreak to transform into an epidemic and consequently into a pandemic owing to the adaptability of microorganisms through a series of molecular and cellular systems (Wani et al., 2022a). Although, humans have somewhat resisted the earlier outbreaks with the cooperation of immune cells and vaccination processes (Jaskuła and Lange, 2020). However, new strains of different families continue to emerge and evolve. The pathogens evade the immune system through different immunoevasory mechanisms. These evasory mechanisms target the immune system which suppresses the antigen presentation, induces cytokine storm, and impairs the interferon response (Kikkert, 2020). This is significant in viral infections and thus it becomes problematic to control and treat such infections. As metagenomics has the potential to identify previously unknown and unidentified microorganisms, it can prove to be an important tool for discovery of new pathogens, evolution and their control before the infection caused by such microbes turns into a pandemic like the SARS-CoV-2 (Temmam et al., 2014). Metagenomics is a versatile approach with applications in diverse fields. It is used to study microbial communities in environments, human microbiomes, agriculture, biotechnology, food safety, clinical diagnostics, ecology, and conservation. It contributes to research in evolutionary biology, phylogenetics, forensics, wastewater treatment, biological oceanography, epidemiology, drug discovery, and more (Azli et al., 2022, Wani et al., 2023a, Zieliński et al., 2022). Metagenomics allows for a comprehensive understanding of the genetic diversity and functions of microbial communities in various contexts, making it a valuable tool in modern science. Viral metagenomics is a cutting-edge method for studying viruses in environmental samples, offering significant advantages over traditional culturable techniques. By directly sequencing the genetic material of viruses in a sample, it allows for unbiased discovery, uncovering both known and unknown viruses, thereby expanding our understanding of viral diversity (Hall et al., 2014, Ogunbayo et al., 2023, Pichler et al., 2023, Van Borm et al., 2020). Additionally, this approach provides valuable ecological insights by revealing the roles of viruses in various ecosystems, including their influence on nutrient cycling and microbial population control (Garza and Dutilh, 2015, Wani et al., 2022b). It enables the characterization of complete viral genomes, aiding in our understanding of viral evolution and function. Moreover, viral metagenomics offers rapid results and avoids bias towards culturable viruses, making it an invaluable tool in diverse fields, from ecology and virology to public health and the study of zoonotic diseases through a One Health approach (Akhtar et al., 2022, Arkhipova et al., 2018).

The SARS-CoV-2 is testimony of these dangerous and deadly viral infections. Soon after the outbreak, research about its evolutionary relationship and molecular studies gained momentum around the world. Coronaviruses are single-stranded viruses that belong to Coronaviridae family with a positive-sense RNA genome of 26–32 kb size (Masters, 2006). The CoV infection of humans is arbitrated between glycoprotein spikes of CoV and the host receptor. The CoV glycoprotein has two subunits, one functioning as a binding domain while another mediates the fusion of the host’s cell membrane and viral membrane (de Wilde et al., 2018). It has been established that most of these outbreaks originate from animals (zoonotic) like Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) in 2002 and 2012 respectively (Ye et al., 2020). This makes viral assemblage and their sequence investigation very important to build a response strategy. The conventional analysis is driven by cell culturing, PCR amplification, immunological and serological testing, hybridization, and microscopy. However, these techniques are often complex, robust, and time-consuming (Houldcroft et al., 2017). Thus virome and microbiome can be well studied, analyzed, and investigated by metagenomic studies supported by the next-generation sequencing techniques.The changing attributes of enveloped viruses are often challenging in developing therapeutic and/or vaccination strategies against such viruses (Anasir and Poh, 2019). This makes active epidemiological studies in animals even more important well before the possible disease outbreak. The metagenomics strategy supported by rapid NGS techniques thus provides a vital tool for the discovery of new pathogens and enables us to understand the dynamics of evolution (Bovo et al., 2017). The metagenomics vigilance strategy must be adopted for the identification of novel species of pathogens. Thus regular scrutiny of possible hotspots like markets, zoos, etc. should be ensured to control viral outbreaks like SARS-CoV-2 (Nieuwenhuijse and Koopmans, 2017). Metagenomics coordinated by the computational tools has helped enormously in understanding the molecular biology of coronaviruses. Some of the recently developed computational tools provided a deeper insight into the functional annotation of the viral genome and helped in understanding the evolutionary relationship of HCoV-2 with other coronaviruses. The key topics covered in this review include the utilization of metagenomics in the surveillance of wildlife populations and intermediate hosts, elucidating the role of environmental factors in zoonotic transmission, and tracking the evolution and adaptation of zoonotic viruses within reservoir hosts. Furthermore, we discuss recent advances in sequencing, bioinformatics tools and analytical methods that facilitate the interpretation of metagenomic data in the context of zoonotic viral infections.