Immunopathology of galectin-3: an increasingly promising target in COVID-19.

Abstract

The pandemic brought on by the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has become a global health crisis, with over 22 million confirmed cases and 777,000 fatalities due to coronavirus disease 2019 (COVID-19) reported worldwide. The major cause of fatality in infected patients, now referred to as the "Cytokine Storm Syndrome" (CSS), is a direct result of aberrant immune activation following SARS-CoV2 infection and results in excess release of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor α (TNF-α), and IL-6, by macrophages, monocytes, and dendritic cells. Single cell analysis has also shown significantly elevated levels of galectin 3 (Gal-3) in macrophages, monocytes, and dendritic cells in patients with severe COVID-19 as compared to mild disease. Inhibition of Gal-3 reduces the release of IL-1, IL-6, and TNF-α from macrophages in vitro, and as such may hold promise in reducing the incidence of CSS. In addition, Gal-3 inhibition shows promise in reducing transforming growth factor ß (TGF-ß) mediated pulmonary fibrosis, likely to be a major consequence in survivors of severe COVID-19. Finally, a key domain in the spike protein of SARS-CoV2 has been shown to bind N-acetylneuraminic acid (Neu5Ac), a process that may be essential to cell entry by the virus. This Neu5Ac-binding domain shares striking morphological, sequence, and functional similarities with human Gal-3. Here we provide an updated review of the literature linking Gal-3 to COVID-19 pathogenesis. Dually targeting galectins and the Neu5Ac-binding domain of SARS-CoV2 shows tentative promise in several stages of the disease: preventing viral entry, modulating the host immune response, and reducing the post-infectious incidence of pulmonary fibrosis.

• Authors: John L Caniglia, Swapna Asuthkar, Andrew J Tsung, Maheedhara R Guda, Kiran K Velpula
• Journal: F1000Research (F1000Res) Vol. 9 Pg. 1078 ( 2020) ISSN: 2046-1402 [Electronic] England
• PMID: 33082935 (Publication Type: Journal Article, Review)
• Copyright: Copyright: © 2020 Caniglia JL et al.

Chemical References

• Galectin 3
• N-Acetylneuraminic Acid

Topics

• Betacoronavirus
• COVID-19
• Coronavirus Infections (pathology)
• Cytokine Release Syndrome (virology)
• Galectin 3 (immunology)
• Humans
• N-Acetylneuraminic Acid
• Pandemics
• Pneumonia, Viral (pathology)
• SARS-CoV-2