The coronavirus, like other viruses, contains all the information necessary for replication, multiplication, and propagation encoded in its genome. Peter Medawar, the English immunologist and writer, aptly defined a virus “as a piece of bad news wrapped up in protein”. The Covid-19 pandemic has been driven by the coronavirus, SARS-CoV-2, which emerged from Wuhan, China, in late 2019, and quickly spread all over the world. This spherical virus, a complex, lifeless chemical entity, springs to life and multiplies once it infects a host cell and subverts the cellular biochemical machinery to serve its own ends of replication and propagation. The coronavirus may have emerged from an animal host. However, in crossing the zoonotic barrier while jumping to humans, it faces many challenges in adapting to an unfamiliar and often hostile host. Finding an appropriate receptor, invariably a host protein on the surface of human cells, is its first task. Its next step will be to use this bridgehead on the cell surface to penetrate the defences of the host cell membrane, forcing entry to deliver its cargo of genetic material, ribonucleic acid (RNA), in the case of the pandemic virus. The spike protein, which dots the surface of the spherical viral particle, is the Trojan Horse, welcomed by a cell surface receptor on human cells and aided by host proteins in breaching the membrane barrier. The virus encounters challenges on its way to finding its host cell, most frequently antibodies, a key component of the human immune response to a foreign microbial invader, which can intercept the virus before it reaches its destination. The nature of this immune response may be conditioned by past encounters with similar viruses. This immune interception is, of course, mediated by very specific chemical interactions that permit the antibody to recognize the foreign virus. Molecular recognition in biology is often characterized by exquisite specificity, a feature which led the famous German chemist, Emil Fischer, to invoke the metaphor of “locks and keys,” well over a century ago. This chapter is confined to the consideration of the evolution of the surface glycoprotien during the pandemic as it provides a striking example of sequence adaption as the virus evolves in diverse human hosts, with genetically determined immune responses that may differ over time periods when human populations have been immunised with different vaccines.