University of Tabriz Journal of Zoonotic Diseases 2476-535X 10 2 2026 06 01 Barriers to cross-species viral transmission: Molecular mechanisms and ecological factors 1130 1149 21726 10.22034/jzd.2026.21726 EN Varuni Bhardwaj Centre for Computational Biology and Bioinformatics, Central University of Himachal Pradesh, Dharamshala, India Journal Article 2026 02 23 Viral host jumps, the process by which viruses adapt to and infect new species, play a crucial role in the emergence of infectious diseases. This phenomenon has been responsible for major outbreaks, including SARS, MERS, HIV, influenza, Ebola, and most recently, COVID-19. Receptor compatibility accounts for 65% of spill over failures between 2000 and 2026, but successful adaptation enables viral replication and sustained disease transmission in new hosts, representing the primary molecular barrier of high-risk ecological interfaces, such as wet markets and livestock farms. Key determinants include viral attachment proteins, such as spike proteins in coronaviruses and hemagglutinin in influenza, which enable receptor binding in new hosts. Additionally, host immune responses, environmental stability, and transmission dynamics influence the likelihood of spillover events. Anthropogenic activities, including deforestation, wildlife trade, and global travel, further increase the risk of viral emergence by facilitating close human-animal interactions. Case studies highlight how habitat disruption and the movement of infected hosts have accelerated pathogen transmission. The COVID-19 pandemic has underscored the devastating consequences of rapid viral emergence, emphasizing the urgent need for enhanced surveillance and robust mitigation strategies. Understanding the molecular and ecological factors driving host jumps is crucial for predicting and mitigating future pandemics. This review explores the mechanisms of viral host jumps, focusing on receptor binding, cellular entry, and ecological barriers. By identifying key determinants of cross-species transmission, specific strategies can be developed to monitor and control emerging viral threats, thus reducing the likelihood of future outbreaks.   https://jzd.tabrizu.ac.ir/article_21726_74c4f9bb767028db381e864cda5b3214.pdf