Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target

Abstract

The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.

SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene

“…It is necessary to understand the characteristic of each SARS-CoV-2 variant to stop the spread of the COVID-19 pandemic. The S gene of SARS-CoV-2 was focused by researchers and pharmaceuticals since it is known that SARS-CoV-2 penetrates via spike protein interacting with ACE2 receptor on the surface of the host cell ( 12 16 20 21 27 ). All effort of vaccine and neutralizing Ab to prevent SARS-CoV-2 infection depends on spike protein alongside some treatment to block viral replication in the host cell.…”

“…COVID-19 vaccines were distributed all over the world since January 2021, with some differences between countries. Mainly, there are 4 types of current COVID-19 vaccines; whole SARS-CoV-2 virus, mRNA, adenovirus, and subunit recombinant protein, which are almost based on the genetic information of spike ( S ) gene on the envelop of SARS-CoV-2 except SARS-CoV-2 viral vaccine ( 19 20 21 22 ). The S gene codes 1,273 amino acid residues with a signal peptide at N-terminus and a single a-helix transmembrane domain following a short cytosolic domain.…”

Aspectos fisiopatológicos envolvidos na sintomatologia da COVID-19 e suas consequências: uma revisão bibliográfica de literatura

“…A proteína S é uma proteína transmembrana composta por 16 subdomínios (SDs), com 22 locais potenciais de glicosilação no domínio extracelular, incluindo um único domínio transmembrana (TM) e uma cauda citosólica (CT), segundo Hong et al (2021), que facilita a ligação do envelope viral aos receptores da enzima conversora de angiotensina 2 (ECA2) expressos nas superfícies das células hospedeiras, principalmente nos pulmões, rins, trato gastrointestinal, coração, fígado e vasos sanguíneos.…”

“…O terceiro domínio funcional conhecido é o RBD, de 227 resíduos de aminoácidos de comprimento e com 2 potenciais sítios de glicosilação. O local mais crítico, com 52 resíduos de aminoácidos, é responsável pela interação com receptores de ECA2 e por permitir a entrada do vírus na célula hospedeira (Hong et al, 2021).…”

An Update on the Pathogenesis of COVID-19 and the Reportedly Rare Thrombotic Events Following Vaccination

“…The transmembrane S2 domain contains the fusion peptide, which mediates the fusion of viral and cellular membranes. 30 , 31 Besides receptor binding, the proteolytic cleavage of coronavirus S proteins by host cell-derived proteases is essential to permit this fusion. SARS-CoV-2 has been shown to use the cell-surface serine protease TMPRSS2 for priming and entry of the virus.…”