SARS-CoV-2 better known as Covid-19 sent the world into a global pandemic. In order to create a vaccine, it was essential to understand how SARS-CoV-2 infected us.
The enzyme angiotensin converting enzyme 2 (ACE2) is attached to our cell membranes bound to a receptor binding domain (RBD) [1]. The spike protein of SARS-CoV-2 enters our bodies and binds to the RBD, allowing the spike protein access to ACE2 and our host cells [2]. Once the spike protein has access to our host cells, it is able to further infect our cells and spread the virus throughout our bodies, causing us to get sick. In order to create an effective vaccine, the pathway between the spike protein and the RBD needs to be interrupted.
It all starts at the ACE2 receptor, but what is that? Let's investigate!
Figure Legend: The coolest image of this protein EVAH and it was handmade!!![3].
Figure Legend:Figure 3:The use of the De Novo protein design to create the LCB inhibitors.
Function
Mechanism
Active Site
Inhibitor Differences
↑Borkotoky S, Dey D, Hazarika Z. Interactions of angiotensin-converting enzyme-2 (ACE2) and SARS-CoV-2 spike receptor-binding domain (RBD): a structural perspective. Mol Biol Rep. 2023 Mar;50(3):2713-2721. PMID:36562937 doi:10.1007/s11033-022-08193-4
↑Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022 Jan;23(1):3-20. PMID:34611326 doi:10.1038/s41580-021-00418-x
↑ 3.03.1Hunt AC, Case JB, Park YJ, Cao L, Wu K, Walls AC, Liu Z, Bowen JE, Yeh HW, Saini S, Helms L, Zhao YT, Hsiang TY, Starr TN, Goreshnik I, Kozodoy L, Carter L, Ravichandran R, Green LB, Matochko WL, Thomson CA, Vögeli B, Krüger A, VanBlargan LA, Chen RE, Ying B, Bailey AL, Kafai NM, Boyken SE, Ljubetič A, Edman N, Ueda G, Chow CM, Johnson M, Addetia A, Navarro MJ, Panpradist N, Gale M Jr, Freedman BS, Bloom JD, Ruohola-Baker H, Whelan SPJ, Stewart L, Diamond MS, Veesler D, Jewett MC, Baker D. Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice. Sci Transl Med. 2022 May 25;14(646):eabn1252. PMID:35412328 doi:10.1126/scitranslmed.abn1252
