FIGURE 1.

Road map of development of cryo-electron microscopy field. Milestones indicated with blue flags starting from development of electron microscope (1931), visualization of first virus under EM (1939), electron diffraction of frozen, hydrated catalase crystals (1974) and development of electron microscopy of frozen biological samples (1983). Then low resolution cryo-EM maps were reconstructed during early 2000. With the development of direct electron detectors around 2011-2013 there was an upsurge of high resolution cryo-EM structures. In 2017 the Nobel Prize in Chemistry was given to the three pioneers (Jacques Dubochet, Joachim Frank, Richard Henderson) for the development of structure determination by cryo-electron microscopy. By the year 2020 atomic resolution (1.22Å) structure was achieved for apoferritin (EMD-11638) by cryo-EM. Green flags indicate the important milestones of the contributions of cryo-EM in bacteriophages (EMD-1086; 5003), HIV Envelope (EMD-5779; 5019) and SARS-CoV2 spike (EMD-21375; 11494) structure determination, the three topics that are the focus of this paper.