ABSTRACT
Viral infection compromises specific organelles of the cell and readdresses its functional resources to satisfy the needs of the invading body. Around 70% of the coronavirus positive-sense single-stranded RNA encodes proteins involved in replication, and these viruses essentially take over the biosynthetic and transport mechanisms to ensure the efficient replication of their genome and trafficking of their virions. Some coronaviruses encode genes for ion-channel proteins - the envelope protein E (orf4a), orf3a and orf8 - which they successfully employ to take control of the endoplasmic reticulum-Golgi complex intermediate compartment or ERGIC. The E protein, which is one of the four structural proteins of SARS-CoV-2 and other coronaviruses, assembles its transmembrane protomers into homopentameric channels with mild cationic selectivity. Orf3a forms homodimers and homotetramers. Both carry a PDZ-binding domain, lending them the versatility to interact with more than 400 target proteins in infected host cells. Orf8 is a very short 29-amino-acid single-passage transmembrane peptide that forms cation-selective channels when assembled in lipid bilayers. This review addresses the contribution of biophysical and structural biology approaches that unravel different facets of coronavirus ion channels, their effects on the cellular machinery of infected cells and some structure-functional correlations with ion channels of higher organisms.
Subject(s)
Computational Chemistry , Ion Channels/chemistry , SARS-CoV-2/chemistry , Viral Proteins/chemistry , COVID-19/virology , Protein ConformationABSTRACT
The current COVID-19 pandemic is caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). By late October 2020, more than 43 million cases of infections, including over 1.15 million deaths, have been confirmed worldwide. This review focuses on our current understanding of SARS-CoV-2 from the perspective of the three-dimensional (3D) structures of SARS-CoV-2 viral proteins and their implications on therapeutics development against COVID-19.
Subject(s)
COVID-19 Drug Treatment , COVID-19/epidemiology , Antibodies, Viral/chemistry , Genome, Viral , Humans , Ion Channels/chemistry , Protein Conformation , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistryABSTRACT
The SARS-CoV-2 3a protein is a putative ion channel implicated in virus life cycle and pathogenesis. We recently expressed, purified, and reconstituted 3a into lipid nanodiscs to solve its structure by cryo-EM to 2.1Å resolution. In this chapter, we describe methods we developed in order to facilitate the study of this protein in other laboratories. We emphasize factors that enabled rapid progression from gene sequence to reconstituted protein (3 weeks in the case of 3a) and provide general observations and tips for adapting these protocols to other membrane proteins of interest.
Subject(s)
Ion Channels/chemistry , Nanostructures , SARS-CoV-2/chemistry , Viral Envelope Proteins/chemistry , Viroporin Proteins/chemistry , Lipid Bilayers/chemistryABSTRACT
The SARS-CoV-2 virus has spread around the world. At this time, there is no vaccine that can help people prevent the spread of coronavirus. We are proposing amantadine as a drug that can be used to mitigate the effects of the virus. It is demonstrated by docking models how amantadine can exert its action on Coronavirus viroporin E.