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Virology . Defining diverse spike-receptor interactions involved in SARS-CoV-2 entry: Mechanisms and therapeutic opportunities

tetano

Editor, Senior Moderator
Virology


. 2025 Mar 21:607:110507.
doi: 10.1016/j.virol.2025.110507. Online ahead of print. Defining diverse spike-receptor interactions involved in SARS-CoV-2 entry: Mechanisms and therapeutic opportunities

Michael Anderson[SUP] 1 [/SUP], Julian Lopez[SUP] 1 [/SUP], Maya Wyr[SUP] 1 [/SUP], Peter W Ramirez[SUP] 2 [/SUP]



Affiliations
Free article Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus that caused the Coronavirus Disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike glycoprotein binds to angiotensin converting enzyme 2 (ACE2) on host cells to facilitate viral entry. However, the presence of SARS-CoV-2 in nearly all human organs - including those with little or no ACE2 expression - suggests the involvement of alternative receptors. Recent studies have identified several cellular proteins and molecules that influence SARS-CoV-2 entry through ACE2-dependent, ACE2-independent, or inhibitory mechanisms. In this review, we explore how these alternative receptors were identified, their expression patterns and roles in viral entry, and their impact on SARS-CoV-2 infection. Additionally, we discuss therapeutic strategies aimed at disrupting these virus-receptor interactions to mitigate COVID-19 pathogenesis.

Keywords: Alternate receptors; Attachment factors; COVID-19; Coronavirus; SARS-CoV-2; Spike protein; Virus entry.

 
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