# Lessons Learnt from COVID-19: Computational Strategies for Facing Present and Future Pandemics
## 1 The COVID-19 Pandemic
### Drug Repurposing  
Considering that bringing a brand-new drug on the market is usually a very long and expensive process [28], the so-called \"drug repurposing\" was the first approach to finding suitable therapeutic options for COVID-19 patients [29,30]. This strategy extends the applicability domain of already marketed drugs for treating diseases other than the one it was conceived for [31]. This approach is appealing because it involves using derisked compounds, with potentially lower overall development costs and shorter development timelines [32]. Unfortunately, despite all the promising premises [33], this approach was largely unsuccessful [34]. Indeed, several investigated drugs showed little to no efficacy in randomized clinical trials [34]. The few successful cases were primarily symptomatic treatments, mostly limited to hospital usage for the most severe cases due to the therapy's high costs or route of administration [35].  
Failure of the drug repurposing strategy against COVID-19 can be mostly traced to the very first stages of the pandemic, where few clinical pieces of evidence were available for the rational elaboration of therapy plans. For example, the combination of HIV protease inhibitors Lopinavir and Ritonavir was examined [36], despite a suboptimal predicted recognition pattern towards the SARS-CoV-2 main protease (M\({}^{\text{PPO}}\)) compared to other compounds of the same class [37]. Another example is the combined use of an antimalarial drug (hydroxychloroquine) and an antibiotic (azithromycin) despite no clear indication of the possible mechanism of action [38,39].  
With more and more clinical observations becoming available, more fine-tuned treatments, especially symptomatic ones, were adopted. This is the case, for example, of corticosteroids such as dexamethasone [40], employed to tame the inflammatory response associated with severe COVID-19 cases, and low molecular weight heparins [41], used to prevent or treat thrombo-embolic events associated caused by interference with the cardiorespiratory system.  
A group of antiarthritis drugs represents another successful example of drug repurposing to their ability to modulate the immune response [42] and cytokine storm [43] caused by severe SARS-CoV-2 infection. This family includes the monoclonal antibodies Tocilizumab [44] and Sarilumab [45], which both inhibit Interleukin-6 (IL-6) signaling; Anakinra [46], which interferes instead with IL-1 signaling; and the Janus Kinase (JAK) inhibitor Baricitinib [47], alone or in conjunction with Remdesivir [48], with the latest representing maybe the most successful example of drug repurposing against COVID-19 being the first approved drug against this illness [49].  
Originally designed against Ebola virus, Remdesivir is a nucleotide analog prodrug that acts as a viral polymerase inhibitor [50] and is efficient in shortening the recovery time in hospitalized adult patients affected by COVID-19 [51]. Unfortunately, as previously mentioned, Remdesivir and the other repurposed drugs need parenteral administration, thereby limiting their massive-scale adoption as pharmacological treatments against COVID-19 [35].