The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a renewed interest in studying the role of the spike S glycoprotein in regulating coronavirus infections in the natural host. Taking advantage of the cryo-electron microscopy structure of SARS-CoV-2 S trimer in the prefusion conformation, we performed a virtual screening simulation with the aim to identify novel molecules that could be used as fusion inhibitors. The spike glycoprotein structure has been completed using modeling techniques and its inner cavity, needful for the postfusion transition of the trimer, has been scanned for the identification of strongly interacting available drugs. Finally, the stability of the protein-drug top complexes has been tested using classical molecular dynamics simulations. The free energy of interaction of the molecules to the spike protein has been evaluated through the MM/GBSA method and per-residue decomposition analysis. Results have been critically discussed considering previous scientific knowledge concerning the selected compounds and sequence alignments have been carried out to evaluate the spike glycoprotein similarity among the betacoronavirus family members. Finally, a cocktail of drugs that may be used as SARS-CoV-2 fusion inhibitors has been suggested.

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）的出现引起了人们对研究刺突S糖蛋白在调节天然宿主中冠状病毒感染中的作用的新兴趣。利用预融合构象中SARS-CoV-2 S三聚体的低温电子显微镜结构，我们进行了虚拟筛选模拟，目的是鉴定可用作融合抑制剂的新型分子。穗状糖蛋白结构已使用建模技术完成，并且对三聚体的融合后过渡所需的内腔进行了扫描，以鉴定相互作用力强的可用药物。最后，已经使用经典的分子动力学模拟测试了蛋白质-药物顶部复合物的稳定性。通过MM / GBSA方法和每个残基的分解分析，可以评估分子与刺突蛋白相互作用的自由能。考虑到有关所选化合物的先前科学知识，对结果进行了严格的讨论，并进行了序列比对以评估β冠状病毒家族成员之间的尖峰糖蛋白相似性。最后，已经提出了可以用作SARS-CoV-2融合抑制剂的药物混合物。