Comprehensive role of SARS‐CoV‐2 spike glycoprotein in regulating host signaling pathway

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, global public health and the economy have suffered unprecedented damage. Based on the increasing related literature, the characteristics and pathogenic mechanisms of the virus, and epidemiological and clinical features of the disease are being rapidly discovered. The spike glycoprotein (S protein), as a key antigen of SARS-CoV-2 for developing vaccines, antibodies, and drug targets, has been shown to play an important role in viral entry, tissue tropism, and pathogenesis. In this review, we summarize the molecular mechanisms of interaction between S protein and host factors, especially receptor-mediated viral modulation of host signaling pathways, and highlight the progression of potential therapeutic targets, prophylactic and therapeutic agents for prevention and treatment of SARS-CoV-2 infection.

Allosteric Signal within the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein Mediated by a Class 3 Monoclonal Antibody Revealed through Molecular Dynamics Simulations and Protein Residue Networks

“…Inhibitors that target S glycoproteins typically prevent virus−membrane fusion by interfering with the interaction between RBD and ACE2 (see Figure 1b) as analogous to the body carrying an object on the shoulder. 7 This article is licensed under CC-BY-NC-ND 4 Monoclonal antibodies (mAbs) that specifically target the RBD have become the potential alternative treatments due to their overall effectiveness and safety. 8,9 These antibodies function by blocking virus's entry into host cells, thereby preventing infection and limiting viral burden.…”

“…Binding of the trimeric S protein onto ACE2 only occurs when at least one RBD of the S1 subunit from the trimer is elevated and rotated away from the S2 subunit to expose its receptor-binding surface. , Figure a displays a 3D structure of an RBD protein that resembles an outward-facing human body, along with nomenclatures of the protein regions for parts of the body. Inhibitors that target S glycoproteins typically prevent virus–membrane fusion by interfering with the interaction between RBD and ACE2 (see Figure b) as analogous to the body carrying an object on the shoulder …”

“…Inhibitors that target S glycoproteins typically prevent virus–membrane fusion by interfering with the interaction between RBD and ACE2 (see Figure 1 b) as analogous to the body carrying an object on the shoulder. 7 …”