Unmasking the Viral Future: Genomic Surveillance and Evolutionary Arms Races in Emerging Pathogens

The 21st century has experienced an alarming increase in viral outbreaks, highlighting critical vulnerabilities in global health systems. The remarkable evolutionary plasticity of RNA viruses—driven by high mutation rates, recombination, and reassortment—enables rapid host cell adaptation and immune evasion, as dramatically illustrated by the recent emergences of SARS-CoV-2, highly pathogenic avian influenza, and novel arboviruses. While next-generation sequencing and bioinformatics now empower real-time genomic surveillance and phylodynamic reconstructions during epidemics, significant challenges remain in predicting which viral lineages will successfully exploit host cellular machinery to cross species barriers and ignite sustained transmission. The intricate and often neglected interactions among viral genomic determinants, host immune and physiological states, and anthropogenic environmental changes—such as deforestation and climate shifts—create a complex and dynamic risk landscape. The immense genetic diversity harbored within wildlife reservoirs acts as a perpetual source of future threats, demanding integrated, proactive research strategies that bridge the virus-host interface across human, animal, and environmental contexts.

Despite unprecedented technological advances in genomic sequencing and bioinformatics, the global scientific community remains largely reactive rather than proactive in addressing emerging viral threats. Current surveillance efforts are often fragmented, poorly coordinated, and heavily biased toward pathogens that have already caused significant human outbreaks, leaving vast reservoirs of viral diversity in wildlife and domestic animals largely unexplored. This reactive paradigm fails to anticipate viral spillover events or to identify high-risk lineages and their host-interaction determinants before they acquire pandemic potential. Furthermore, the vast amount of genomic data generated during outbreaks is frequently underutilized due to a lack of standardized analytical frameworks and limited integration with host response, immunological, ecological, and clinical datasets.

This Research Topic aims to shift the paradigm from reactive outbreak response to proactive pandemic preparedness by deepening our understanding of the specific virus-host interactions that drive species jumps and outbreak emergence — not virus-host biology in general. We invite contributions that: (i) characterize the genomic diversity and evolutionary trajectories of emerging viruses and the specific molecular determinants that expand host range or enable cross-species transmission; (ii) develop and apply novel bioinformatics tools and machine learning approaches for real-time genomic surveillance and for flagging host-adaptive mutations linked to transmission fitness and outbreak risk; (iii) elucidate the molecular mechanisms of host cell entry and immune evasion specifically where they represent a rate-limiting step for spillover or sustained transmission; and (iv) integrate genomic data with host response, immunological, and ecological information to build predictive models of viral emergence and outbreak risk. By fostering collaborative efforts across disciplines and geographic boundaries, this Research Topic will generate the foundational knowledge and tools needed to anticipate — not just respond to — future viral epidemics.

We particularly welcome submissions addressing the following themes:

Genomic Diversity and Evolution Linked to Emergence: Studies investigating viral genetic variability, phylodynamics, recombination, and reassortment specifically as they shape host range expansion, tropism shifts, and cross-species transmission potential.

Molecular Drivers of Species Jumps and Outbreak Potential: Investigations into how emerging viruses manipulate host cellular pathways or evade immune responses specifically at the point of crossing into a new host or gaining sustained transmission — for example, adaptive mutations in receptor-binding or immune-antagonist genes that mark a transition from spillover to epidemic spread. General characterization of host-virus interactions or immune evasion in already-established human pathogens is outside scope.

Novel Methodologies for Risk Prediction: Development or application of sequencing technologies, bioinformatics pipelines, machine learning, and statistical models designed to identify or predict adaptive mutations with functional significance for host-range expansion, immune evasion tied to emergence, or outbreak risk — not general-purpose genomic characterization tools.

Genomic Determinants of Outbreak Trajectory: Investigations into virulence, tropism, and persistence factors specifically where they explain why a lineage did or did not progress toward sustained transmission or pandemic spread, rather than pathogenesis in isolated, endemic pathogens.

Ecological and Anthropogenic Drivers of Spillover: Studies examining how ecological and environmental factors (e.g., land-use change, climate shifts, wildlife-human contact) shape the molecular evolution of cross-species transmission potential and could inform early-warning surveillance.

We encourage submissions on a broad range of human and animal viral pathogens — including but not limited to coronaviruses, influenza viruses, poxviruses, hemorrhagic fever viruses, arboviruses, picornaviruses, and hepatitis viruses — provided the work is framed around outbreak or pandemic potential rather than general virology.