SARS-Cov2 protease with boceprevir
The whole of the 16 non structural proteins (nsp) of cov2 are produced in one run. This giant protein has to be cut into its functional parts. This requires a special protease aware of the proper cuts to perform. Speciality on the other hand means a target for manmade inhibitors. For other human pathogenic viruses inhibitors were developed, some of which could stop also multiplication of cov2 in cell cultures. Here is shown the inhibition mechanism of boceprevir which was successfully used in treating HCV-infections.
The atoms of the cov2 protease are shown as blue spheres. We are interested in the region binding the giant protein with its prospective cutting sites . If we have a look into the binding pocket , we recognize a lot of charged atoms (red = oxygen = negative; blue = nitrogen = positive) in the side branches of the protein chain.
What to do to prevent the protease to perform its essntial work for the propagation of the virus? We may plug the binding pocket so no protein can bind and gets cleaved. Boceprevir is known to inhibit HCV, it fits also here . For a permanent plug the molecule has to be bound long enough in its position . Boceprevir contains oxygen and nitrogen atoms, so there are hydrogen bridges to the binding pocket , in these places . Most important is a true chemical bond between a sulphur atom (side chain of cysteine145) and the carbon backbone of boceprevir . In the study cited below a bunch of substances with known inhibition of other viruses were investigated. Besides only one other molecule only boceprevir inhibited the cov2 protease . Boceprevir is allowed to treat HCV illness, but covid19 is something different. The effect found in cell cultures may be not strong enough to start human experiments. But there is a way to further investigate.
L Fu et al, Nature Communications 11, 4417 (2020), DOI 10.1038/s41467-020-18233-x
A structural formula you may find at wikipedia.