Timing of antiviral treatment initiation is critical to reduce SARS-Cov-2 viral load

Antonio Gonçalves; Julie Bertrand; Ruian Ke; Emmanuelle Comets; Xavier de Lamballerie; Denis Malvy; Andrés Pizzorno; Olivier Terrier; Manuel Rosa Calatrava; France Mentré; Patrick Smith; Alan S Perelson; Jérémie Guedj

. Given their pharmacokinetic and 179 pharmacodynamic properties (Table 1) , we calculated a mean antiviral efficacy of up to 66% 180 for lopinavir/ritonavir, 18% for IFN-β-1a, and 33% for hydroxychloroquine. Given these 181 estimates, these compounds are unlikely to have a dramatic effect on peak viral load if 182 administered after the onset of symptoms. In fact, the effective concentrations will 183 presumably be lower in patients, as relevant drug may be further limited by protein binding 184 (in particular for lopinavir, which has a protein binding rate > 98%) or capability to penetrate 185 respiratory compartments, which is not well characterized. Importantly, levels of antiviral 186 efficacy of ~50% could nonetheless be relevant in a prophylactic setting, before symptom 187 onset, to reduce viral replication in the upper respiratory tract and reduce the risk of large 188 infiltration to the lung before an effective immune response is mounted to clear virus [2] 189 Note, above we calculated the effectiveness of drugs administered in monotherapy for their 190 usual dosing regimen. We also did not consider drugs that could directly target infected cells 191 and lead to their elimination, such as some monoclonal antibodies. 192