**4. Conclusions**

In summary, the relatively conserved elements of the viral life cycle offer many opportunities to reexamine compounds developed to address previous outbreaks for efficacy against novel outbreaks. Clear examples are shown in the results against non-structural proteins above, which often maintain significantly higher sequence homology across species due to a conserved mechanism than structural proteins. However, while this sequence conservation indeed leads to a degree of "cross-talk" between nsp inhibitors, the required exquisite and intricate nature of the interaction between a successful drug and its target will almost inevitably reduce the efficacy of a monotherapy. As a result, it is likely that while repurposing can identify promising candidates, care must be taken not to hope for a single effective solution in existing drugs (e.g. Ivermectin, hydroxychloroquinine, etc.). Rather, functional (clinical) solutions are much more likely be found in careful clinical trials of combination therapies of drugs identified through repurposing screens.

The current combination of virtual, *in vitro* and *in vivo* screening is well positioned to perform rapid repurposing experiments on the relatively small number of clinically approved candidate molecules. However, significant research effort should be expended globally to continue to identify potential viral inhibitors and further populate the potential repurposing list.

Response speed is a key factor facing outbreaks. Drug repurposing is a practical solution that provides multiple benefits beyond classical drug discovery. Perhaps the greatest advancement in this area has been the improvements in computational techniques, that has developed in parallel with advances in structural biology—both of which continue to improve. These structural views of the proteins driving disease expand the number of experiments that can be performed *in silico*, providing both an increase in speed of hypothesis generation, as well as an important pre-filter stage to select out candidate molecules for screening. In our opinion a key aspect that should not be overlooked is the *in vitro* validation of a molecular effect on a proposed target. Certain recent experiences have shown that attempts to bypass this stage and short-cut the process by directly jumping into clinical trials can produce conflicting results, leading to confusion and loss of confidence of the public. However, despite successful application of drug repurposing, no single golden standard as yet exists to give relatively predictable results.
