The coronavirus pandemic has had a huge impact on public health with over 165 million people infected, 3.4 million deaths and a hugely deleterious effect on most economies. While vaccination effectively protects against the disease it is likely that viruses will evolve that can replicate in hosts immunised with the present vaccines. Thus, there is a great unmet need for effective antivirals that can block the development of serious disease in infected patients. The seven papers published in this issue of the Biochemical Journal address this need by expressing and purifying components required for viral replication, developing biochemical assays for these components and using the assays to screen a library of pre-existing pharmaceuticals for drugs that inhibited the target in vitro and inhibited viral replication in cell culture. The candidate drugs obtained are potential antivirals that may protect against SARS-CoV-2 infection. While not all the antiviral candidates will make it through to the clinic, they will be useful tool compounds and can act as the starting point for further drug discovery programmes.

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**Figure?1.. Coronavirus non-structural proteins (nsps).**
(A) The N-terminal region of the polyprotein showing the two viral proteases (blue) with green arrows indicating the sites of cleavage mediated by the nsp3 papain-like protease (PL^pro) and sites of cleavage of the nsp5 chymotrypsin-like protease (also known as 3CLpro or Main protease Mpro) in red. (B) The capping complex and replication transcription complex with the associated uridine specific endoribonuclease nsp15. Components studied in the drug discovery studies [1–7] indicated in blue.

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An all-out assault on SARS-CoV-2 replication

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