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. 2020 Aug 4;32(2):145–147. doi: 10.1016/j.cmet.2020.07.006

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© 2020 Elsevier Inc.

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Drug Repurposing for COVID-19 and Beyond

(A) Promising repurposed drugs for COVID-19 presented on a theoretical time versus severity graph. Blue represents the COVID-19 cases in which a mortality benefit has been demonstrated for dexamethasone (hospitalized patients on supplemental oxygen therapy or ventilation). Gray represents the COVID-19 cases in which a surrogate outcome benefit has been demonstrated for remdesivir (greater benefit if given earlier in disease course). Red represents the COVID-19 cases in which observational studies have suggested a potential mortality benefit for statins and famotidine (hospitalized patients). Like statins, a well-matched retrospective cohort study of famotidine suggested improved outcomes in hospitalized COVID-19 patients (Freedberg et al., 2020).

(B) A conceptual framework for drug repurposing. Drug repurposing candidates are preliminarily identified through laboratory investigation of drug targets, mining of published literature, and high-throughput drug screens. While the success rate of high-throughput drug screens has been low historically, the basic understanding of SARS-CoV-2 biology, as well as the large number of efforts, likely increases the potential for success. These candidates can be validated and refined through orthogonal in vitro and in vivo studies. Observational studies of widely used drugs are often performed to search for associations between drug exposure and outcomes. In this case, the observational study by Zhang et al. provided the first indication that statins may be effective in COVID-19 (red border highlights this aspect of the framework). Open-label, single-arm, or preferably, randomized controlled trials are then performed to investigate efficacy (and safety) and determine if the drug should be adopted in clinical practice and/or given regulatory approval for the new indication. In parallel, it is important to track all drugs being used off-label and experimentally to identify promising candidates for further investigation. The CORONA Project tracks off-label and experimental drugs used in COVID-19 (red box). There is very high interest in drug repurposing for COVID-19 from multiple sectors, including the US Food & Drug Administration (FDA), which will likely speed up the time from candidate identification to approval.