SARS-CoV-2 is a kind of ‘smart’ virus that generates complex and dynamic crosstalk with hosts. Even with thousands of publications, the researchers have only uncovered the ‘iceberg’ of the virus-infectious properties as well as its effects on human beings, and the approaches against the virus and the related pandemic are limited. In this special issue, several latest publications provide new insights into the relationship between SARS-CoV-2 and its hosts and also deliver potential methods to fight the infectious disease.