H2020Индивидуална стипендия2022–2024

CoVentry · Multiscale study of the interactions between corona viruses of various pathogenicity and cell membrane components in the early stages of virus entry

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2022-05-23 → 2024-05-22
Финансиране от ЕС: 191 852 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Взаимодействията между протеина „спайк“ на коронавирусите и компонентите на клетъчната мембрана, като захарта хепаран сулфат, се анализират в естествената им среда. Това помага да се разбере по-точно как вирусите се закрепят и проникват в човешките клетки.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Multiscale study of the interactions between corona viruses of various pathogenicity and cell membrane components in the early stages of virus entry

Understanding how viruses attach to and enter h ost cells is critical in the study of infectious diseases. This attachment process is the first step in viral infection and plays a key role in determining how effectively a virus can spread. Viruses bind to a membrane molecule which is needed for viral entry, referred as viral receptor. In the case of SARS-CoV-2, this interaction is mediated by the viral protein spike. However, the cellular membrane is a complex environment comprised of hundreds of molecular species, which the virus has to navigate to reach the receptor. To do so, viruses also establish weak and transient bonds to several additional molecules. Heparan sulfate (HS), a complex sugar molecule found on the surface of human cells, is known to be exploited as an attachment factor by various viruses. SARS-CoV-2 spike has been shown to interact with HS and the strength of this interaction to vary among the variants that emerged during the pandemic. Traditionally, studies of molecular interactions are performed using isolated molecular species. Researchers often purify the spike protein and the viral receptor and measure the strength of the bond formed between them. However, this method does not accurately represent the complex environment a virus encounters when approaching a cell. In reality, the viral particle simultaneously interacts with several membrane components, whose relevance and interplay cannot be fully appreciated when studied separately. This creates a significant gap between the biophysical characteristics determined in these studies and the actual biological question. The CoVentry project calls for a paradigm shift in studying biophysical interactions during viral entry. By focusing on the interaction between the spike protein and the complete host cell membrane, the project aimed to understand the role of various membrane components in regulating viral attachment and entry and their potential effects on virus tropism (the ability of a virus to infect particular cell types).

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Coronaviruses (CoV) have been responsible for several severe viral outbreaks culminating in the current global pandemic. However, some viruses of this family are widespread and only cause mild conditions, like the common cold. The origin of the significant variation in the severity of the CoV-related diseases is still poorly understood. Recent studies have suggested that the strength of the interaction between the virus and the cell surface during the early stages of virus entry could play an important role. CoVs attachment to the plasma membrane is mediated by the specific interaction between the viral spike glycoprotein (CoV-S) and receptors found on the cell surface. In addition, several CoVs have been shown to interact with the cellular glycocalyx during the early attachment to the cell surface. In this proposal, I describe the study of the early entry mechanism of CoV-SARS, CoV-SARS2, and hCoV-NL63 which all target the same cellular receptor, angiotensin-converting enzyme 2, while strongly varying in their pathogenicity. The study focuses on the dynamics, kinetics and strength of the interaction of these viruses with the cell surface. It employs an incremental approach, from the study of the bond between individual CoV-S and single membrane components to multivalent interactions between the virion and the cell surface. A wide array of biophysical (e.g. single-particle tracking, and optical tweezer) and biological (e.g. viral pseudotypes) techniques are used, combining the host’s and my expertise. This multidisciplinary project will result in a unique and comprehensive characterisation of the interactions taking place during CoV-entry, it will elucidate the difference between viral species, and it will give insights into the origin of the observed differences in pathogenicity. In addition, this work will strengthen and expand my experience and network in the virology and biophysics fields, significantly improving my career prospects as an independent researcher.

Оригинален текст от CORDIS (на английски).

Участници

UMEA UNIVERSITET · UMEAКоординаторШвеция