ABSTRACT
SARS-CoV-2 has mutually illuminated our collective knowledge and knowledge gaps, particularly in antiviral defense and therapeutic strategies. A recent study in Science (Poirier et al., 2021) uncovers an ancient antiviral mechanism that mammals utilize to suppress viruses, including SARS-CoV-2 and Zika virus, that could have broad implications for therapeutic strategies.
Subject(s)
Argonaute Proteins/metabolism , COVID-19/prevention & control , Interferons/immunology , RNA Interference/physiology , Ribonuclease III/metabolism , Zika Virus Infection/prevention & control , Animals , Cell Line , HEK293 Cells , Humans , RNA, Small Interfering/genetics , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Virus Replication , Zika Virus/genetics , Zika Virus/immunologyABSTRACT
In late 2019, the betacoronavirus SARS-CoV-2 was identified as the viral agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. Coronaviruses Spike proteins are responsible for their ability to interact with host membrane receptors and different proteins have been identified as SARS-CoV-2 interactors, among which Angiotensin-converting enzyme 2 (ACE2), and Basigin2/EMMPRIN/CD147 (CD147). CD147 plays an important role in human immunodeficiency virus type 1, hepatitis C virus, hepatitis B virus, Kaposi's sarcoma-associated herpesvirus, and severe acute respiratory syndrome coronavirus infections. In particular, SARS-CoV recognizes the CD147 receptor expressed on the surface of host cells by its nucleocapsid protein binding to cyclophilin A (CyPA), a ligand for CD147. However, the involvement of CD147 in SARS-CoV-2 infection is still debated. Interference with both the function (blocking antibody) and the expression (knock down) of CD147 showed that this receptor partakes in SARS-CoV-2 infection and provided additional clues on the underlying mechanism: CD147 binding to CyPA does not play a role; CD147 regulates ACE2 levels and both receptors are affected by virus infection. Altogether, these findings suggest that CD147 is involved in SARS-CoV-2 tropism and represents a possible therapeutic target to challenge COVID-19.