2 spike protein have been generated and selectively bind to the S1 domain (including those that target the receptor-binding domain) or S2 domain. Aptamer-based reagents can also be made that can bind to the spike protein from both SARS-CoV and SARS-CoV-2 with comparable affinity. Some of these reagents potently inhibit the binding of the spike protein to its cell-surface receptor ACE2 and exhibit antiviral activity against SARS-CoV-2 virus, including many of the recent variants. Heterodimerization of modified aptamers that target nonoverlapping epitopes is a viable strategy for improving potency and reducing the impact of mutations on drug efficacy. Aptamers have several advantages for the treatment of COVID-19, including lower production costs than antibodies, no need for a cold chain, and the ability to be delivered by inhalation.Preparing Therapeutics for the Next PandemicThe WHO International Health Regulations obliges countries to have “the capacity to respond promptly and effectively to public health risks and public health emergencies of international concern” (Article 13) (107). However, what this looks like is in the eye of the beholder and the perceived importance of pandemic preparedness will wane over time. There are numerous aspects to consider.First, data from localized epidemics needs to be disseminated quickly, especially outbreaks of unknown diseases. The accelerated distribution of viral genomic sequences is critical to the development of diagnostics and therapeutics, especially vaccines.There is a need to ensure existing patient datasets are ready to examine therapeutic hypotheses early in pandemics. OpenSAFELY, a platform that allows secure analysis of 24 million records in the UK National Health Service (7, 108, 109) provided insights into patient outcomes and the effect of concomitant medication use on COVID-19 outcomes, for example, nonsteroidal anti-inflammatory drug use and ICS. Similarly, large-scale global registries are equally important in providing information on preexisting medication use. Data from registries such as the COVID-19 Global Rheumatology Alliance and Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) helped to identify the ineffectiveness of hydroxychloroquine as a prophylactic therapy for infection with SARS-CoV2 (110) and the potential importance of therapies targeting TNF and IL-6 (111–115).There is a need to prioritize vaccine and therapeutic research into agents with known pandemic potential, such as influenza, dengue, chikungunya, and hemorrhagic fever viruses like Ebola and Marburg. The burden from these agents disproportionately lies in low to middle income countries where surveillance and health infrastructure is least well-equipped to manage outbreaks.Finally, creating a clinical trials system that is ready to deploy within days is critical to address important questions in therapeutics. The enthusiasm to fund extensive trial networks will undoubtedly wane in time, unless they either can address other important questions between pandemics, such as influenza, or only consume a very small resource to maintain their capacity between pandemics.Conclusion This pandemic has put a strain on the global community that we have not seen outside wartime. In our interconnected world, we have seen that none of us are safe until we are all safe. Inevitably, the response has been incomplete, but in contrast to previous respiratory viral threats, we have seen progress in therapeutics and an extraordinary vaccine response.Nevertheless, to keep pace with evolving unmet needs, drug development must adapt. Despite our improved knowledge of biology and inflammatory processes, most of the therapeutic approaches have been empiric. Future pandemic threats are inevitable and require a more focused response; we must translate biological insight into specific therapeutic hypotheses for testing. Thousands of small underpowered studies of myriad therapeutics have not delivered much insight. Targeted repurposing of existing therapeutics is vital in the early response to an emerging threat, but there needs to be an effective trial ecosystem to bring forward promising novel therapies.We also must think beyond our current, limited field-of-view. Most of the current response has focused on preventing death in hospitalized patients. Effective treatments for earlier disease that can be deployed widely to prevent hospitalization have eluded us; oral and inhaled routes of delivery are important for mass deployment. These treatments are particularly important for less-wealthy countries in which hospital infrastructure is limited. Most conditions require combination therapy and we need to consider how the armamentarium can be used to maximal effect; this is likely to involve combining antiviral and immunomodulatory drugs. SARS-CoV-2 targeted antivirals are a clear gap, but host-directed antivirals and interventions based on specific cellular aspects of the inflammatory response may also be important. Host-directed antivirals may be particularly important because they are likely to have utility against many other viruses, and thus may prevent an epidemic turning into a pandemic.Pandemics require a rapid coordinated response (Box 1). Maintaining extensive research and