  Small molecule drugs have an important role to play in combating viral
infections, and biophysics support has been central for contributing to the
discovery and design of direct acting antivirals. Perhaps one of the most
successful biophysical tools for this purpose is NMR spectroscopy when utilized
strategically and pragmatically within team workflows and timelines. This
report describes some clear examples of how NMR applications contributed to the
design of antivirals when combined with medicinal chemistry, biochemistry,
X-ray crystallography and computational chemistry. Overall, these
multidisciplinary approaches allowed teams to reveal and expose compound
physical properties from which design ideas were spawned and tested to achieve
the desired successes. Examples are discussed for the discovery of antivirals
that target HCV, HIV and SARS-CoV-2.
