Abstract

The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CL^pro and PL^pro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PL^pro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CL^pro, and PL^pro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.

Communicated by Ramaswamy H. Sarma

摘要

当前大流行的 SARS-CoV-2 已在世界范围内造成了严重破坏，目前既没有药物也没有疫苗可以治疗这种疾病。因此，迫切需要能够对抗这种致命感染的新型疗法。在这项研究中，我们报告了天青蛋白及其肽的治疗评估：p18 和 p28 针对病毒结构 S 蛋白和非结构 3CL ^pro和 PL ^pro蛋白。在分析的复合物中，与其他病毒蛋白相比，天青蛋白与 S 蛋白的 S2 结构域的对接相对较好。衍生肽 p18 与 PL ^pro的活性位点结构域结合蛋白质; 然而，在其他复合体中，记录到的相互作用较少。第二个天青蛋白衍生肽 p28 在对接的蛋白质中表现最好。p28 通过与 S 蛋白、3CL ^pro和 PL ^pro形成几个静电和氢键，与所有三种病毒蛋白和宿主 ACE-2 受体相互作用。MD 模拟表明 p28 对 S 蛋白和 ACE-2 受体表现出很强的亲和力，表明 p28 作为蛋白质-蛋白质相互作用抑制剂的可能性。我们的数据表明 p28 具有作为抗 SARS-CoV-2 试剂的潜力，可以进一步利用以建立其在治疗当前和未来 SARS-CoV 危机中的有效性。

由 Ramaswamy H. Sarma 交流