Effective therapies for COVID-19 are urgently needed. Presently there are more than 800 COVID-19 clinical trials globally, many with drug combinations, resulting in an empirical process with an enormous number of possible combinations. To identify the most promising potential therapies, we developed a biophysical model for the SARS-CoV-2 viral cycle and performed a sensitivity analysis for individual model parameters and all possible pairwise parameter changes (16² = 256 possibilities). We found that model-predicted virion production is fairly insensitive to changes in most viral entry, assembly, and release parameters, but highly sensitive to some viral transcription and translation parameters. Furthermore, we found a cooperative benefit to pairwise targeting of transcription and translation, predicting that combined targeting of these processes will be especially effective in inhibiting viral production.

中文翻译：

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SARS-CoV-2病毒周期的生物物理模型揭示了理想的抗病毒靶标

迫切需要有效的COVID-19疗法。目前，全球有800多项COVID-19临床试验，其中许多是药物组合的，导致了经验过程中有大量可能的组合。为了确定最有希望的潜在疗法，我们开发了SARS-CoV-2病毒周期的生物物理模型，并对单个模型参数和所有可能的成对参数变化进行了敏感性分析（16 ²= 256种可能性）。我们发现，模型预测的病毒粒子生产对大多数病毒进入，装配和释放参数的变化相当不敏感，但对某些病毒转录和翻译参数高度敏感。此外，我们发现转录和翻译的成对靶向具有合作优势，并预测这些过程的联合靶向在抑制病毒产生方面将特别有效。