The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD–ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.

最近被称为 2019 年冠状病毒病 (COVID-19) 的严重急性呼吸系统综合症传播得如此迅速和严重，以致世界卫生组织 (WHO) 宣布对新的冠状病毒 SARS-CoV-2 大流行进入紧急状态。尽管有几个国家选择了几乎完全的封锁来减缓 SARS-CoV-2 的传播，但科学界被要求通过确定诊断和治疗危险的 COVID-19 的新工具来应对毁灭性的爆发。出于这个目的，我们进行了计算机比较建模分析，从而获得了对 SARS-CoV-2 刺突蛋白在受体结合域 (RBD) 水平上发生的主要构象变化的新见解，以及与人体细胞血管紧张素转换酶 2 (ACE2) 受体，有利于人体细胞入侵。此外，我们的分析提供了（1）一个理想的管道来识别可能针对 SARS-CoV-2 刺突 RBD 的已表征抗体，旨在防止与人类 ACE2 的相互作用，以及（2）构建新的可能中和抗体的说明，根据已识别的现有抗体的化学/物理空间限制和互补决定区 (CDR) 诱变。所提出的抗体在计算机上显示出对 SARS-CoV-2 刺突 RBD 的高亲和力，并且可以用作参考抗体，也可用于构建针对当前和未来冠状病毒的新高亲和力抗体，这些冠状病毒能够通过其刺突蛋白与人类的相互作用侵入人类细胞ACE2。更一般地说，