Recent progress of surface plasmon resonance in the development of coronavirus disease-2019 drug candidates

Abstract

At the end of 2019, the new coronavirus caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suddenly raged, bringing a severe public health crisis to the world. It is urgent to discover suitable drugs and treatment regimens against this coronavirus disease 2019 (COVID-19) and related diseases. Based on the previous knowledge and experience in treating similar diseases, researchers have come up with hundreds of possible drug candidates in the shortest possible time. Based on surface plasmon resonance (SPR) technology, this review summarized the application of SPR technology in COVID-19 research from four aspects: the invasion mode of SARS-CoV-2 into host cells, antibody drug candidates for the treatment of COVID-19, small molecule drug repurposing and vaccines for COVID-19. SPR technology has gradually become a powerful tool to study the interaction between drugs and targets due to its high efficiency, automation, labeling-free and high data resolution. The use of SPR technology can not only obtain the affinity data between drugs and targets, but also clarify the binding sites and mechanisms of drugs. We hope that this review can provide a reference for the subsequent application of SPR technology in antiviral drug development.

Current Trends in SPR Biosensing of SARS-CoV-2 Entry Inhibitors

“…They belong to the subfamily Coronavirinae that includes four genera (alpha (α)-, beta (β)-, gamma (γ)-and delta (δ)-CoVs) [32,33]. Coronaviruses usually contain canonical structural proteins open reading frames (ORF) 1a and 1b, E (envelope protein), M (membrane protein), N (nucleocapsid protein) and S (spike protein) and some accessories proteins such as the membrane-anchored HE (hemagglutinin-esterase) protein expressed by betacoronaviruses [6]. Amongst this genus, SARS-CoV, MERS-CoV and SARS-CoV-2 are considered the most pathogenic human betacoronaviruses.…”

“…The S protein is not only responsible for giving the virus the appearance of a crown [35] but also in facilitating both the attachment and the entry into the host cells. Specifically, subunit S1 plays an important role in recognizing ACE2 receptors since it contains the N-terminal domain (NTD), the receptor binding domain (RBD) and two conserved subdomains (SD1 and SD2) [6]. On the other hand, subunit S2 mediates the process of membrane fusion.…”

“…Novel drug discovery strategies rely on the high throughput screening of different classes of antiviral agents [5]. For example, the increase of antibody drug candidates has provided an efficient approach to treat viral infections due to their specificity [6,7]. However, this selectivity is directed against specific antigens thus limiting their spectrum of activity.…”

“…SPR sensorgrams provide the association, equilibrium and dissociation phases observed after the injection of the analyte onto the immobilized bioreceptor surface [5,23]. By monitoring binding interactions, SPR biosensors inform on the association (Ka) and dissociation rates (Kd), equilibrium dissociation constants (KD) and stoichiometry of the interacting biomolecules depending on their binding affinity [6,8,24]. The kinetic information supplied by SPR biosensors is particularly useful for the rapid screening of drug candidates such as virus entry inhibitors.…”

“…The role of SPR biosensors in pharmaceutical analysis and viral diagnosis has previously explored [5,8,19,20,26]. However, the specific utility of SPR biosensor high-throughput screening of viral inhibitors in the current pandemic context ha been sufficiently addressed [5,6]. Therefore, the aim of this work is to compile recen velopments of SPR biosensor approaches in targeting SARS-CoV-2 entry into host This review specifically concentrates on the identification and prioritization of viral in itors through the characterization of their binding and kinetic parameters.…”