Background SARS-CoV-2 developed global-pandemic with millions of infections/deaths. As it is urgently necessary it is assumed that some blockers/inhibitors of ACE2 could be helpful to resist the binding of viral-spike Receptor-Binding-Domain (RBD). Methods Here, conserved RBD from 186-countries were compared with WUHAN-Hu-1 wild-type (CLUSTAL-X2/Pymol). The RBD of ACE2-bound nCOV2 crystal-structure 6VW1 was analyzed by Haddock-PatchDock. Extensive structural study/trial to introduce point/double/triple mutations in the different locations of CUT4 (most-effective from total 4 proposed fragments; CUTs) were tested with Swiss-Model-Expacy. Results Blind-docking of mutated-CUTs in ACE2 completely rejected the nCOV2 binding to ACE2. Further, competitive-docking/binding-analyses (by PRODIGY) demonstrated few more bonding (LYS31-PHE490 and GLN42-GLN498) of CUT4 (than wild) and hindered TYR41-THR500 interaction with ACE2. Moreover, mutated-CUT4 even showed higher blocking effect against spike-ACE2 binding. Conclusion In summary, CUT4-mutant rejects whole glycosylated-nCoV2 in all pre-dock, post-dock and competitive-docking conditions. The present work strategy is relevant because it could be able to block at the first level entry of the virus to the host cells. Supplementary Information The online version contains supplementary material available at 10.1186/s41231-022-00109-5.
【저자키워드】 SARS CoV-2 pandemic, ACE2 blocking by RBD fragments, Mutation in RBD, T500S, Haddock and Hawkdock, 【초록키워드】 SARS-CoV-2, ACE2, Mutation, virus, RBD, binding, Interaction, host cells, supplementary material, wild-type, Result, tested, analyzed, conserved, demonstrated, conditions, assumed, 【제목키워드】 SARS-CoV-2, ACE2, Mutation, in silico, RBD, S-protein, fraction, viral spike, block, conserved, significantly,