Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia.
J Biomol Struct Dyn. 2021 Jul;39(11):4175-4184. doi: 10.1080/07391102.2020.1775123. Epub 2020 Jun 9.
SARS coronavirus (COVID-19) is a real health challenge of the 21st century for scientists, health workers, politicians, and all humans that has severe cause epidemic worldwide. The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). Docking studies were designed in order to obtain the binding energies for Plantaricin metabolites. The binding energies for Plantaricin W were -14.64, -11.1 and -12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. Plantaricin W, D, and JLA-9 were able to block the residues (THR556, ALA558) surrounding the deep grove catalytic site (VAL557) of RdRp making them more therapeutically active for COVID-19. Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.Communicated by Ramaswamy H. Sarma.
严重急性呼吸综合征冠状病毒(COVID-19)是 21 世纪科学家、卫生工作者、政治家和全人类面临的真正健康挑战,它在全球范围内造成了严重的流行。该病毒通过机制发挥其致病活性,并通过刺突蛋白(S)和血管紧张素转换酶 2(ACE2)受体蛋白进入宿主细胞。本工作是通过益生菌(即植物乳杆菌 BN、植物乳杆菌 JLA-9、植物乳杆菌 W 和植物乳杆菌 D)及其 RNA 依赖性 RNA 聚合酶(RdRp)对刺突蛋白(S)和 ACE2 受体上的残余结合蛋白(RBP)进行计算靶标阻断的一种尝试。设计了对接研究以获得植物乳杆菌代谢物的结合能。植物乳杆菌 W 与聚合酶、RBD 和 ACE2 的结合能分别为-14.64、-11.1 和-12.68,与其他化合物相比非常高。植物乳杆菌 W、D 和 JLA-9 能够阻断 RdRp 酶深沟催化位点(VAL557)周围的残基(THR556、ALA558),使它们对 COVID-19 更具治疗活性。分子动力学研究进一步加强了植物乳杆菌 w 与 SARS-CoV-2 RdRp 酶、刺突蛋白 RBD 和人 ACE2 受体复合物的稳定性。本研究提出了多种选择,既可以阻断 S 蛋白上的 RBD,也可以阻断 S 蛋白与 ACE2 受体蛋白的相互作用,还可以通过抑制 RdRp 来对抗 COVID-19 的任何影响,为 COVID-19 的治疗开辟了一条道路,直到有更好的治疗方法出现。由 Ramaswamy H. Sarma 交流。