Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics

• DOI: 10.3389/fmicb.2022.1013911
• Publication Date: 2022-10-18T05:07:35Z
• Authors: Jun-Feng Cao; Xingyu Yang; Li Xiong; Mei Wu; Shengyan Chen; Chenyang Xiong; Peiyong He; Yonghua Zong; Lixin Zhang; Hongjiao Fu; Yue Qi; Xiran Ying; Dengxin Liu; Xiaosong Hu; Xiao Zhang
• Keywords: Docking (animal); KEGG

Purpose 2019 Coronavirus disease (COVID-19) has caused millions of confirmed cases and deaths worldwide. TMPRSS2-mediated hydrolysis maturation spike protein is essential for SARS-CoV-2 infection in vivo . The latest research found that a TMPRSS2 inhibitor called N-0385 could effectively prevent the its variants. However, it not clear about mechanism treatment COVID-19. Therefore, this study used computer simulations to investigate COVID-19 by impeding infection. Methods GeneCards database was search gene targets, core targets were analyzed PPI, GO KEGG. Molecular docking molecular dynamics validate analyze binding stability small molecule target proteins. supercomputer platform simulate number hydrogen bonds, free energy, at residue level, radius gyration solvent accessible surface area. Results There 4,600 from database. KEGG analysis indicated signaling pathways immune response inflammation played crucial roles showed block treat acting on ACE2, NLRP3. demonstrate form very stable bindings with TLR7. Conclusion investigated simulation. We speculated may only inhibit invasion directly TMPRSS2, ACE2 DPP4, but also recognition process inflammatory regulating TLR7, NLRP3 IL-10 invasion. these results suggested act through multiple reduce damage responses.