Modelling SARS-CoV-2 Dynamics: Implications for Therapy

Kwang Su Kim; Keisuke Ejima; Yusuke Ito; Shoya Iwanami; Hirofumi Ohashi; Yoshiki Koizumi; Yusuke Asai; Shinji Nakaoka; Koichi Watashi; Robin N Thompson; Shingo Iwami

infections. This can be induced by drugs including human neutralising antibodies, 140 viral entry-inhibitors and/or antibodies raised by vaccination (13, 14) . For example, a 141 SARS-CoV-specific human monoclonal antibody has been reported to cross react 142 with SARS-CoV-2 (14). We conducted in silico experiments with varying drug 143 efficacy (considering inhibition rates from 10% to 100%, i.e. 0.1 ≤ ≤ 1) and with the 144 timing of initiation of therapy from 0 days (i.e., post-exposure prophylactic use of 145 antivirals) until 5 days after symptom onset (i.e., 0 ≤ * ≤ 5) (see Methods). Our 146 results show that early initiation of therapy (especially within two to three days) with 147 even a relatively weak drug (inhibition rates as low as 50%) might effectively reduce 148 the area under the curve of viral load (AUC) and prevent significant reductions in the 149 numbers of target cells because of cytopathic effects due to cell invasion. A therapy 150 of this type initiated four days after symptom onset, on the other hand, is not 151 predicted to induce a clear antiviral effect (Fig. 3AD) . This suggests that blocking de 152 novo infections is not likely to be effective unless the intervention is initiated before 153 the peak viral load. Hence, appropriate initiation timing (i.e., before or very soon after 154 symptom onset) is an important factor for suppressing viral load in addition to the 155 therapy having the potential for antiviral effects. 156