Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

Abstract

COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the RBD activity of the S protein by blocking the RBD interaction with hACE2, which makes the glycosylated S protein a potential target for designing and developing antiviral agents. In this study, the molecular features of the S protein of SARS-CoV-2 are highlighted, such as the structures, functions, and interactions of the S protein and ACE2. Additionally, computational tools developed for the treatment of COVID-19 are provided, for example, algorithms, databases, and relevant programs. Finally, recent advances in the novel development of antivirals against the S protein are summarized, including screening of natural products, drug repurposing and rational design. This study is expected to provide novel insights for the efficient discovery of promising drug candidates against the S protein and contribute to the development of broad-spectrum anti-coronavirus drugs to fight against SARS-CoV-2.

Targeting SARS-CoV-2 and host cell receptor interactions

“…These efforts have cumulated in a number of small molecules and natural products that can interfere with Spike-ACE2 binding. These discoveries have been comprehensively covered in past reviews ( Liu et al, 2021 ; Ma et al, 2021 ; Xiang et al, 2021 ). Nevertheless, some of the compounds from these screens await further validations with binding or biophysical assays, or virus neutralisation assays, to confirm their mechanism of actions, as well as their broad-spectrum anti-CoV activity.…”

Epidemiological features, genomic characteristics, and origin tracing of the COVID‐19 outbreaks in Beijing from January to September 2022

“…The spike protein is located on the surface of the SARS-CoV-2 virus and plays an important role in virus attachment and entrance into host cells. 19 Omicron variants shared a considerable number of mutations (Figure 4). More than 30 mutations have been found…”

Anti-SARS-CoV-2 Activity of Ampelozizyphus amazonicus (Saracura-Mirá): Focus on the Modulation of the Spike-ACE2 Interaction by Chemically Characterized Bark Extracts by LC-DAD-APCI-MS/MS

“…In silico analyses provided valuable and reliable information on a range of substances with potential anti-SARS-CoV-2 activity in a relatively short time; these are currently being tested in in vitro and in vivo assays [ 18 , 19 , 20 , 21 , 22 ]. Despite viral enzymatic inhibition being the main mechanism of action for most of the currently available and in development antivirals, blockage of SP interaction with ACE2 is becoming an attractive approach for a new generation of antivirals since it has the potential to hamper viral recognition and infection of host cells, preventing viral propagation inside the organism as well as contributing to a reduced mutation rate and thus the appearance of new variants [ 23 ].…”