# Evolutionary Insight into Fatal Human Coronaviruses (hCoVs) with a Focus on Circulating SARS-CoV-2 Variants Under Monitoring (VUMs)

## TL;DR

This review explores the evolution of deadly human coronaviruses, focusing on SARS-CoV-2 variants, to better understand their spread and impact on public health.

## Contribution

The paper provides an updated evolutionary analysis of SARS-CoV-2 variants under monitoring as of May 2025 using advanced bioinformatics and visualization techniques.

## Key findings

- Key spike protein substitutions in the RBD are linked to increased transmissibility and immune evasion.
- Real-time genomic surveillance is critical for tracking and mitigating emerging variant risks.
- Evolutionary insights help identify viral elements important for vaccine and therapeutic development.

## Abstract

The breach of an interspecies barrier by RNA viruses has facilitated the emergence of lethal hCoVs, particularly SARS-CoV-2, resulting in significant socioeconomic setbacks and public health risks globally in recent years. Moreover, the high evolutionary plasticity of hCoVs has led to the continuous emergence of diverse variants, complicating clinical management and public health responses. Studying the evolutionary trajectory of hCoVs, which provides a molecular roadmap for understanding viruses’ adaptation, tissue tropism, spread, virulence, and immune evasion, is crucial for addressing the challenges of zoonotic spillover of viruses. Tracing the evolutionary trajectory of lethal hCoVs provides essential genomic insights required for risk stratification, variant/sub-variant classification, preparedness for outbreaks and pandemics, and the identification of critical viral elements for vaccine and therapeutic development. Therefore, this review examines the evolutionary landscape of the three known lethal hCoVs, presenting a focused narrative on SARS-CoV-2 variants under monitoring (VUMs) as of May 2025. Using advanced bioinformatics approaches and data visualization, the review highlights key spike protein substitutions, particularly within the receptor-binding domain (RBD), which drive transmissibility, immune escape, and potential resistance to therapeutics. The article highlights the importance of real-time genomic surveillance and intervention strategies in mitigating emerging variant/sub-variant risks within the ongoing COVID-19 landscape.